B-Cells Extracellular Vesicles Shape Melanoma Response to Immune Checkpoint Therapy

The immune tumor microenvironment (TME) is increasingly recognized as a dynamic ecosystem where B cells play pivotal roles in modulating therapeutic responses, particularly in the context of immune checkpoint blockade (ICB) therapy. While B cells have traditionally been viewed as bystanders in tumor...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Al Hrout, Ala’a, Balayev, Agshin, Cervantes-Gracia, Karla, Gkelis, Konstantinos, Benke, Stephan, Matínez Gómez, Julia M., Silina, Karina, Levesque, Mitchell P., Chahwan, Richard
Format Paper
LanguageEnglish
Published Cold Spring Harbor Laboratory 16.12.2024
Edition1.1
Subjects
Cancer Biology
Online AccessGet full text
ISSN2692-8205
DOI10.1101/2024.12.12.628150

Cover

Abstract The immune tumor microenvironment (TME) is increasingly recognized as a dynamic ecosystem where B cells play pivotal roles in modulating therapeutic responses, particularly in the context of immune checkpoint blockade (ICB) therapy. While B cells have traditionally been viewed as bystanders in tumor immunity, recent evidence suggests they may actively influence anti-tumor immunity, albeit with conflicting reports regarding their pro-tumor or anti-tumor roles. This study explores the crucial roles played by B cells and their secreted extracellular vesicles (EVs) in shaping melanoma responses to ICB therapy. We show a significant enrichment of B cells in ICB therapy responders compared to non-responders, pre-treatment, through retrospective analyses of melanoma patient tumors. Functional assays demonstrate that B cell depletion impairs T cell-mediated tumor cytotoxicity, underscoring the importance of B cells in anti-tumor responses. To investigate the clinical relevance, EVs were isolated from melanoma patient tumors, and fractioned into tumor and immune subpopulations. MiRNA profiling of CD19+ EVs identifies miR-99a-5p as a top candidate, among several others, upregulated in responders. Functional assays show that miR-99a-5p silencing in B cells diminishes T cell-mediated anti-tumor activity, suggesting its role in promoting B cell-mediated immune responses. Mechanistically, miR-99a-5p influences B cell maturation within the TME by mediating class-switch recombination. Our findings highlight the important role of B cells and their derived EVs in shaping the efficacy of melanoma immunotherapy, paving the way for novel therapeutic strategies targeting B cell-related pathways.
AbstractList The immune tumor microenvironment (TME) is increasingly recognized as a dynamic ecosystem where B cells play pivotal roles in modulating therapeutic responses, particularly in the context of immune checkpoint blockade (ICB) therapy. While B cells have traditionally been viewed as bystanders in tumor immunity, recent evidence suggests they may actively influence anti-tumor immunity, albeit with conflicting reports regarding their pro-tumor or anti-tumor roles. This study explores the crucial roles played by B cells and their secreted extracellular vesicles (EVs) in shaping melanoma responses to ICB therapy. We show a significant enrichment of B cells in ICB therapy responders compared to non-responders, pre-treatment, through retrospective analyses of melanoma patient tumors. Functional assays demonstrate that B cell depletion impairs T cell-mediated tumor cytotoxicity, underscoring the importance of B cells in anti-tumor responses. To investigate the clinical relevance, EVs were isolated from melanoma patient tumors, and fractioned into tumor and immune subpopulations. MiRNA profiling of CD19+ EVs identifies miR-99a-5p as a top candidate, among several others, upregulated in responders. Functional assays show that miR-99a-5p silencing in B cells diminishes T cell-mediated anti-tumor activity, suggesting its role in promoting B cell-mediated immune responses. Mechanistically, miR-99a-5p influences B cell maturation within the TME by mediating class-switch recombination. Our findings highlight the important role of B cells and their derived EVs in shaping the efficacy of melanoma immunotherapy, paving the way for novel therapeutic strategies targeting B cell-related pathways.
Author Matínez Gómez, Julia M.
Benke, Stephan
Gkelis, Konstantinos
Chahwan, Richard
Cervantes-Gracia, Karla
Silina, Karina
Levesque, Mitchell P.
Al Hrout, Ala’a
Balayev, Agshin
Author_xml – sequence: 1
  givenname: Ala’a
  surname: Al Hrout
  fullname: Al Hrout, Ala’a
  organization: Institute of Experimental Immunology, University of Zurich
– sequence: 2
  givenname: Agshin
  surname: Balayev
  fullname: Balayev, Agshin
  organization: Institute of Experimental Immunology, University of Zurich
– sequence: 3
  givenname: Karla
  surname: Cervantes-Gracia
  fullname: Cervantes-Gracia, Karla
  organization: Institute of Experimental Immunology, University of Zurich
– sequence: 4
  givenname: Konstantinos
  surname: Gkelis
  fullname: Gkelis, Konstantinos
  organization: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich)
– sequence: 5
  givenname: Stephan
  surname: Benke
  fullname: Benke, Stephan
  organization: Flow Cytometry Facility, University of Zurich
– sequence: 6
  givenname: Julia M.
  surname: Matínez Gómez
  fullname: Matínez Gómez, Julia M.
  organization: Department of Dermatology, University Hospital Zurich, University of Zurich
– sequence: 7
  givenname: Karina
  orcidid: 0000-0003-3947-2710
  surname: Silina
  fullname: Silina, Karina
  organization: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich)
– sequence: 8
  givenname: Mitchell P.
  surname: Levesque
  fullname: Levesque, Mitchell P.
  organization: Department of Dermatology, University Hospital Zurich, University of Zurich
– sequence: 9
  givenname: Richard
  orcidid: 0000-0002-8672-7790
  surname: Chahwan
  fullname: Chahwan, Richard
  email: chahwan@immunology.uzh.ch
  organization: Institute of Experimental Immunology, University of Zurich
BookMark eNotkEFLwzAYhoMoOOd-gLccvXTm-9qky1HL1MFEcMVrSbOvtNompelk-_daJjzwvqfn8NywS-cdMXYHYgkg4AEFJkvACYUrkOKCzVBpjFYo5DVbhPAlhECtIE6TGds9RRm1beDr4zgY-3cPrRn4J4XGthT4rjY98TdqjfOd4R8Ueu8C8dHzTdcdHPGsJvvd-8aNPK9pMP3pll1Vpg20-N85y5_XefYabd9fNtnjNipTJSKLiSaL1tgKY6EQkHBf4b6UmBAhVtKWlUlTQCmtTYGMllqXOlEW0IKK5-z-rC0bPxybn6Ifms4Mp2JKUABOnBPEv09GUyY
Cites_doi 10.3389/fcell.2022.866601
10.3389/fimmu.2020.02105
10.1146/annurev.immunol.24.021605.090517
10.1007/s00281-010-0233-9
10.4049/jimmunol.0803773
10.1038/s41586-019-1914-8
10.1126/sciimmunol.abg5003
10.3389/fimmu.2023.1176175
10.1038/S42003-022-04025-0
10.3389/fimmu.2022.955063
ContentType Paper
Copyright 2024, Posted by Cold Spring Harbor Laboratory
Copyright_xml – notice: 2024, Posted by Cold Spring Harbor Laboratory
DBID FX.
DOI 10.1101/2024.12.12.628150
DatabaseName bioRxiv
DatabaseTitleList
Database_xml – sequence: 1
  dbid: FX.
  name: bioRxiv
  url: https://www.biorxiv.org/
  sourceTypes: Open Access Repository
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 2692-8205
Edition 1.1
ExternalDocumentID 2024.12.12.628150v1
GroupedDBID 8FE
8FH
AFKRA
ALMA_UNASSIGNED_HOLDINGS
BBNVY
BENPR
BHPHI
FX.
HCIFZ
LK8
M7P
NQS
PIMPY
PROAC
RHI
ID FETCH-LOGICAL-b760-c249ec2cacf2306212e2df2db524ee22f5cbfa771255cc71ea9599b946c12c163
IEDL.DBID FX.
IngestDate Tue Dec 31 19:38:58 EST 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed false
IsScholarly false
Language English
License This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-b760-c249ec2cacf2306212e2df2db524ee22f5cbfa771255cc71ea9599b946c12c163
Notes Competing Interest Statement: The authors have declared no competing interest.
ORCID 0000-0003-3947-2710
0000-0002-8672-7790
OpenAccessLink https://www.biorxiv.org/content/10.1101/2024.12.12.628150
PageCount 34
ParticipantIDs biorxiv_primary_2024_12_12_628150
PublicationCentury 2000
PublicationDate 20241216
PublicationDateYYYYMMDD 2024-12-16
PublicationDate_xml – month: 12
  year: 2024
  text: 20241216
  day: 16
PublicationDecade 2020
PublicationTitle bioRxiv
PublicationYear 2024
Publisher Cold Spring Harbor Laboratory
Publisher_xml – name: Cold Spring Harbor Laboratory
References Banér, Marits, Nilsson, Winqvist, Landegren (2024.12.12.628150v1.25) 2005; 51
Tsai, Lin, Chou, Lin, Chen, Hwang (2024.12.12.628150v1.31) 2018; 11
Tlaposo, Nijman, willem Stoorvogel, Leijendekker, Hardingfl Cornelis, Melief, Geuze (2024.12.12.628150v1.62)
Chiaruttini, Mele, Opzoomer, Crescioli, Ilieva, Lacy, Karagiannis (2024.12.12.628150v1.12) 2017; 6
Phan, Longjohn, Gormley, Smith, Dang-Lawson, Matsuuchi, Gold, Christian (2024.12.12.628150v1.63) 2021; 207
Cui, Zhou, Zhao, Zhou, Xu, Xu, Zheng, Xue, Xia, Zhang, Ding, Cao, Tian, Shi, He (2024.12.12.628150v1.47) 2012; 12
Xie, Liu, Guo, Guan, Liu, Xie, Jiang, Ma, Zhou (2024.12.12.628150v1.55) 2020; 27
Li, Teitz-Tennenbaum, Donald, Li, Chang (2024.12.12.628150v1.4) 2009
Jerby-Arnon, Shah, Cuoco, Rodman, Su, Melms, Leeson, Kanodia, Mei, Lin, Wang, Rabasha, Liu, Zhang, Margolais, Ashenberg, Ott, Buchbinder, Haq, Hodi, Boland, Sullivan, Frederick, Miao, Moll, Flaherty, Herlyn, Jenkins, Thummalapalli, Kowalczyk, Cañadas, Schilling, Cartwright, Luoma, Malu, Hwu, Bernatchez, Forget, Barbie, Shalek, Tirosh, Sorger, Wucherpfennig, Van Allen, Schadendorf, Johnson, Rotem, Rozenblatt-Rosen, Garraway, Yoon, Izar, Regev (2024.12.12.628150v1.22) 2018; 175
Fridman, Pagès, Sautès-Fridman, Galon (2024.12.12.628150v1.2) 2012; 12
Nelson (2024.12.12.628150v1.6) 2010; 185
Li, Luo, Han, Duan, Wei, Chen (2024.12.12.628150v1.41) 2013; 109
Poggio, Hu, Pai, Chu, Belair, Chang, Montabana, Lang, Fu, Fong, Blelloch (2024.12.12.628150v1.15) 2019; 177
Yim, Al Hrout, Borgoni, Chahwan (2024.12.12.628150v1.26) 2020; 12
Chen, Huang, Zhang, Zhang, Wu, Xu, Yu, Yang, Wang, Sun, Xia, Man, Zhong, Antelo, Wu, Xiong, Liu, Guan, Li, Liu, Yang, Lu, Dong, McGettigan, Somasundaram, Radhakrishnan, Mills, Lu, Kim, Chen, Dong, Zhao, Karakousis, Mitchell, Schuchter, Herlyn, Wherry, Xu, Guo (2024.12.12.628150v1.14) 2018; 560
McLeod, Walker, Patel, Boulougouris, Sansom (2024.12.12.628150v1.23) 1998; 160
Restivo, Tastanova, Balázs, Panebianco, Diepenbruck, Ercan, Preca, Hafner, Weber, Kurzeder, Vetter, Soysal, Beisel, Bentires-Alj, Piscuoglio, Krauthammer, Levesque (2024.12.12.628150v1.66) 2022; 5
Yim, Krzyzaniak, Al Hrout, Peacock, Chahwan (2024.12.12.628150v1.29) 2023; 12
Serafim, Cardoso, Storti, da Silva, Qi, Parasuram, Navegante, Peron, Silva, Espreafico, Paçó-Larson, Price, Valente (2024.12.12.628150v1.57) 2024; 43
Griss, Bauer, Wagner, Simon, Chen, Grabmeier-Pfistershammer, Maurer-Granofszky, Roka, Penz, Bock, Zhang, Herlyn, Glatz, Läubli, Mertz, Petzelbauer, Wiesner, Hartl, Pickl, Somasundaram, Steinberger, Wagner (2024.12.12.628150v1.8) 2019; 10
Juneja, McGuire, Manguso, LaFleur, Collins, Haining, Freeman, Sharpe (2024.12.12.628150v1.17) 2017; 214
Xie, Xu, Lu, Mao, Wang (2024.12.12.628150v1.16) 2019; 18
Holl, O’Connor, Holl, Roney, Zimmermann, Jha, Kelsoe, Ting (2024.12.12.628150v1.56) 2011; 186
Li, Fu, Zeng, Cohen, Li, Chen, Li, Liu (2024.12.12.628150v1.69) 2020; 48
Feliciano, Garcia-Mayea, Jubierre, Mir, Hummel, Castellvi, Hernández-Losa, Paciucci, Sansano, Sun, Ramón, Cajal, Kondon, Soriano, Segura, Lyakhovich, Lleonart (2024.12.12.628150v1.42) 2017; 8
Galon, Mlecnik, Bindea, Angell, Berger, Lagorce, Lugli, Zlobec, Hartmann, Bifulco, Nagtegaal, Palmqvist, Masucci, Botti, Tatangelo, Delrio, Maio, Laghi, Grizzi, Asslaber, D’Arrigo, Vidal Vanaclocha, Zavadova, Chouchane, Ohashi, Hafezi Bakhtiari, Wouters, Roehrl, Nguyen, Kawakami, Hazama, Okuno, Ogino, Gibbs, Waring, Sato, Torigoe, Itoh, Patel, Shukla, Wang, Kopetz, Sinicrope, Scripcariu, Ascierto, Marincola, Fox, Pagès (2024.12.12.628150v1.1) 2014; 232
Chaput, Théry (2024.12.12.628150v1.18) 2011
Singh, Roszik, Saini, Singh, Bavisi, Wang, Vien, Yang, Kundu, Davis, Bover, Diab, Neelapu, Overwijk, Rai, Singh (2024.12.12.628150v1.40) 2022; 13
Liu, Ewald, Pang, Legrand, Jeon, Sangiovanni, Hacariz, Zhou, Head, Basu, Xia (2024.12.12.628150v1.68) 2023; 14
DiLillo, Yanaba, Tedder (2024.12.12.628150v1.9) 2010; 184
Wang, Zhao, Yang, Luo, Zhang, Wang, Liu, Hou, Guo, Song, Guo, Huang (2024.12.12.628150v1.33) 2018; 8
Hossain, Gimenez, Stockwell, Tsai, Print, Rys, Cybulska-Stopa, Ratajska, Harazin-Lechowska, Almomani, Jackson, Chatterjee, Eccles (2024.12.12.628150v1.19) 2022; 13
Martin, Chan (2024.12.12.628150v1.5) 2006
Gutknecht, Holodick, Rothstein (2024.12.12.628150v1.65) 2023; 26
Bolderson, Tomimatsu, Richard, Boucher, Kumar, Pandita, Burma, Khanna (2024.12.12.628150v1.53) 2010; 38
Ansel, Ngo, Hyman, Luther, Förster, Sedgwick, Browning, Lipp, Cyster (2024.12.12.628150v1.39) 2000; 406
Selemenakis, Sharma, Uhrig, Katz, Kwon, Sung, Wiese (2024.12.12.628150v1.52) 2022; 10
Shen, Huang (2024.12.12.628150v1.44) 2012; 12
Mazumder, Gong, Almasan (2024.12.12.628150v1.46) 2000; 19
Al Hrout, Levesque, Chahwan (2024.12.12.628150v1.27) 2023; 14
Li, Heyer (2024.12.12.628150v1.51) 2008; 18
Tang, Li, Kang, Gao, Li, Zhang (2024.12.12.628150v1.73) 2017; 45
Calderón, Schindler, Malin, Schebesta, Sun, Schwickert, Alberti, Fischer, Jaritz, Tagoh, Ebert, Minnich, Liston, Cochella, Busslinger (2024.12.12.628150v1.38) 2021; 6
Iglesia, Parker, Hoadley, Serody, Perou, Vincent (2024.12.12.628150v1.60) 2016; 108
Cobaleda, Schebesta, Delogu, Busslinger (2024.12.12.628150v1.37) 2007; 8
Riaz, Havel, Makarov, Desrichard, Urba, Sims, Hodi, Martín-Algarra, Mandal, Sharfman, Bhatia, Hwu, Gajewski, Slingluff, Chowell, Kendall, Chang, Shah, Kuo, Morris, Sidhom, Schneck, Horak, Weinhold, Chan (2024.12.12.628150v1.21) 2017; 171
Ho, Yim, Borgoni, Chahwan (2024.12.12.628150v1.28) 2022; 1
Helmink, Reddy, Gao, Zhang, Basar, Thakur, Yizhak, Sade-Feldman, Blando, Han, Gopalakrishnan, Xi, Zhao, Amaria, Tawbi, Cogdill, Liu, LeBleu, Kugeratski, Patel, Davies, Hwu, Lee, Gershenwald, Lucci, Arora, Woodman, Keung, Gaudreau, Reuben, Spencer, Burton, Haydu, Lazar, Zapassodi, Hudgens, Ledesma, Ong, Bailey, Warren, Rao, Krijgsman, Rozeman, Peeper, Blank, Schumacher, Butterfield, Zelazowska, McBride, Kalluri, Allison, Petitprez, Fridman, Sautès-Fridman, Hacohen, Rezvani, Sharma, Tetzlaff, Wang, Wargo (2024.12.12.628150v1.11) 2020; 577
Yu, Cao, Shen, Feng (2024.12.12.628150v1.13) 2015; 6
Zhang, Jin, Liu, Iv, Wang, Wang, Liu, Ding, Yang, Li, Zhang, Fu, Xie, Wu, Zhou, Qian (2024.12.12.628150v1.30) 2014; 3
Li, Zheng, Zhang, Zhang, Zhang, Zhang (2024.12.12.628150v1.61) 2022; 12
Seprényi, Shibata, Ónody, Kohsaka (2024.12.12.628150v1.24) 1997; 197
Chen, Tsai, Leone (2024.12.12.628150v1.43) 2009; 9
Long, Shi, Ye, Guo, Zhou, Tang (2024.12.12.628150v1.32) 2020; 9
Chang, Zhou, Soufan, Xia (2024.12.12.628150v1.67) 2020; 48
Rodgers, Mustard, McLean, Hutchison, Pritchard (2024.12.12.628150v1.7) 2022; 35
Cabrita, Lauss, Sanna, Donia, Skaarup Larsen, Mitra, Johansson, Phung, Harbst, Vallon-Christersson, van Schoiack, Lövgren, Warren, Jirström, Olsson, Pietras, Ingvar, Isaksson, Schadendorf, Schmidt, Bastholt, Carneiro, Wargo, Svane, Jönsson (2024.12.12.628150v1.10) 2020; 577
Zona, Bella, Burton, Nestal de Moraes, Lam (2024.12.12.628150v1.54) 2014; 1839
Feng, Li, Stewart, Barbulescu, Desivo, Álvarez-Quilón, Pezo, Perera, Chan, Tong, Mohamad-Ramshan, Berru, Nakib, Li, Kardar, Carlyle, Moffat, Durocher, Di Noia, Bhagwat, Martin (2024.12.12.628150v1.35) 2021; 600
Rada, Williams, Nilsen, Barnes, Lindahl, Neuberger (2024.12.12.628150v1.49) 2002; 12
Metsalu, Vilo (2024.12.12.628150v1.71) 2015; 43
Fuxa, Busslinger (2024.12.12.628150v1.36) 2007; 178
Rakhmanov, Sic, Kienzler, Fischer, Rizzi, Seidl, Melkaoui, Unger, Moehle, Schmit, Deshmukh, Ayata, Schuh, Zhang, Cosset, Verhoeyen, Peter, Voll, Salzer, Eibel, Warnatz (2024.12.12.628150v1.58) 2014; 9
Heberle, Meirelles, da Silva, Telles, Minghim (2024.12.12.628150v1.72) 2015; 16
Enserink, Kolodner (2024.12.12.628150v1.45) 2010; 5
Li, Xu, Chen, Chen, Zhang, Yu, Yao, Chen, Fu, Zhou, Wang (2024.12.12.628150v1.50) 2022; 41
Rival, Mandal, Cramton, Qiao, Arish, Sun, McCann, Dudley, Solga, Erdbrügger, Erickson (2024.12.12.628150v1.64) 2024; 14
Saul, Ilieva, Bax, Karagiannis, Correa, Rodriguez-Hernandez, Josephs, Tosi, Egbuniwe, Lombardi, Crescioli, Hobbs, Villanova, Cheung, Geh, Healy, Harries, Sanz-Moreno, Fear, Spicer, Lacy, Nestle, Karagiannis (2024.12.12.628150v1.59) 2016; 6
Hugo, Zaretsky, Sun, Song, Moreno, Hu-Lieskovan, Berent-Maoz, Pang, Chmielowski, Cherry, Seja, Lomeli, Kong, Kelley, Sosman, Johnson, Ribas, Lo (2024.12.12.628150v1.20) 2016; 165
Petersen, Casellas, Reina-San-Martin, Chen, Difilippantonio, Wilson, Hanitsch, Celeste, Muramatsu, Pilch, Redon, Ried, Bonner, Honjo, Nussenzweig, Nussenzweig (2024.12.12.628150v1.48) 2001; 414
Zhou, Soufan, Ewald, Hancock, Basu, Xia (2024.12.12.628150v1.70) 2019; 47
Maibach, Sadozai, Seyed Jafari, Hunger, Schenk (2024.12.12.628150v1.3) 2020; 11
Holl, O’Connor, Holl, Roney, Zimmermann, Jha, Kelsoe, Ting (2024.12.12.628150v1.34) 2011; 186
References_xml – volume: 27
  start-page: 1383
  year: 2020
  end-page: 1397
  ident: 2024.12.12.628150v1.55
  article-title: RBX1 prompts degradation of EXO1 to limit the homologous recombination pathway of DNA double-strand break repair in G1 phase
  publication-title: Cell Death Differ
– volume: 48
  start-page: W509
  year: 2020
  end-page: W514
  ident: 2024.12.12.628150v1.69
  article-title: TIMER2.0 for analysis of tumor-infiltrating immune cells
  publication-title: Nucleic Acids Res
– volume: 8
  start-page: 463
  year: 2007
  end-page: 470
  ident: 2024.12.12.628150v1.37
  article-title: Pax5: the guardian of B cell identity and function
  publication-title: Nat Immunol
– volume: 175
  start-page: 984
  year: 2018
  end-page: 997
  ident: 2024.12.12.628150v1.22
  article-title: A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade
  publication-title: Cell
– volume: 184
  start-page: 4006
  year: 2010
  end-page: 4016
  ident: 2024.12.12.628150v1.9
  article-title: B Cells Are Required for Optimal CD4+ and CD8+ T Cell Tumor Immunity: Therapeutic B Cell Depletion Enhances B16 Melanoma Growth in Mice
  publication-title: The Journal of Immunology
– volume: 10
  year: 2022
  ident: 2024.12.12.628150v1.52
  article-title: RAD51AP1 and RAD54L Can Underpin Two Distinct RAD51-Dependent Routes of DNA Damage Repair via Homologous Recombination
  publication-title: Front Cell Dev Biol
  doi: 10.3389/fcell.2022.866601
– volume: 11
  year: 2020
  ident: 2024.12.12.628150v1.3
  article-title: Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2020.02105
– volume: 10
  start-page: 1
  issue: 1
  year: 2019
  end-page: 14
  ident: 2024.12.12.628150v1.8
  article-title: B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma
  publication-title: Nature Communications
– year: 2006
  ident: 2024.12.12.628150v1.5
  article-title: B CELL IMMUNOBIOLOGY IN DISEASE: Evolving Concepts from the Clinic
  publication-title: Annu Rev Immunol
  doi: 10.1146/annurev.immunol.24.021605.090517
– volume: 171
  start-page: 934
  year: 2017
  end-page: 949
  ident: 2024.12.12.628150v1.21
  article-title: Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab
  publication-title: Cell
– volume: 600
  start-page: 324
  issue: 7888
  year: 2021
  end-page: 328
  ident: 2024.12.12.628150v1.35
  article-title: FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation
  publication-title: Nature
– volume: 5
  issue: 11
  year: 2010
  ident: 2024.12.12.628150v1.45
  article-title: An overview of Cdk1-controlled targets and processes
  publication-title: Cell Div
– volume: 12
  start-page: 1748
  year: 2002
  end-page: 1755
  ident: 2024.12.12.628150v1.49
  article-title: Immunoglobulin Isotype Switching Is Inhibited and Somatic Hypermutation Perturbed in UNG-Deficient Mice
  publication-title: Current Biology
– volume: 13
  issue: 794684
  year: 2022
  ident: 2024.12.12.628150v1.40
  article-title: B Cells Are Required to Generate Optimal Anti-Melanoma Immunity in Response to Checkpoint Blockade
  publication-title: Front Immunol
– volume: 35
  start-page: 303
  year: 2022
  end-page: 319
  ident: 2024.12.12.628150v1.7
  article-title: A B-cell or a key player? The different roles of B-cells and antibodies in melanoma
  publication-title: Pigment Cell Melanoma Res
– volume: 165
  start-page: 35
  year: 2016
  end-page: 44
  ident: 2024.12.12.628150v1.20
  article-title: Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
  publication-title: Cell
– volume: 9
  issue: 499482
  year: 2020
  ident: 2024.12.12.628150v1.32
  article-title: MicroRNA-99a Suppresses Breast Cancer Progression by Targeting FGFR3
  publication-title: Front Oncol
– volume: 11
  issue: 239
  year: 2018
  ident: 2024.12.12.628150v1.31
  article-title: miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001-induced apoptosis in human urinary bladder urothelial carcinoma cells
  publication-title: Onco Targets Ther
– volume: 178
  start-page: 3031
  year: 2007
  end-page: 3037
  ident: 2024.12.12.628150v1.36
  article-title: Reporter Gene Insertions Reveal a Strictly B Lymphoid-Specific Expression Pattern of Pax5 in Support of Its B Cell Identity Function
  publication-title: The Journal of Immunology
– volume: 108
  start-page: djw144
  year: 2016
  ident: 2024.12.12.628150v1.60
  article-title: Genomic Analysis of Immune Cell Infiltrates Across 11 Tumor Types
  publication-title: J Natl Cancer Inst
– volume: 26
  issue: 107526
  year: 2023
  ident: 2024.12.12.628150v1.65
  article-title: B cell extracellular vesicles contain monomeric IgM that binds antigen and enters target cells
  publication-title: iScience
– volume: 186
  start-page: 5603
  year: 2011
  end-page: 5611
  ident: 2024.12.12.628150v1.56
  article-title: Plexin-D1 Is a Novel Regulator of Germinal Centers and Humoral Immune Responses
  publication-title: The Journal of Immunology
– volume: 12
  start-page: 298
  year: 2012
  end-page: 306
  ident: 2024.12.12.628150v1.2
  article-title: The immune contexture in human tumours: impact on clinical outcome
  publication-title: Nat Rev Cancer
– volume: 160
  start-page: 2072
  year: 1998
  end-page: 2079
  ident: 2024.12.12.628150v1.23
  article-title: Activation of Human T Cells with Superantigen (Staphylococcal Enterotoxin B) and CD28 Confers Resistance to Apoptosis via CD95
  publication-title: The Journal of Immunology
– volume: 6
  start-page: 37151
  year: 2015
  end-page: 37168
  ident: 2024.12.12.628150v1.13
  article-title: Tumor-derived exosomes in cancer progression and treatment failure
  publication-title: Oncotarget
– volume: 12
  start-page: 1
  year: 2012
  end-page: 11
  ident: 2024.12.12.628150v1.47
  article-title: MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma
  publication-title: BMC Cancer
– volume: 414
  start-page: 660
  issue: 6864
  year: 2001
  end-page: 665
  ident: 2024.12.12.628150v1.48
  article-title: AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switching
  publication-title: Nature
– volume: 41
  start-page: 111600
  year: 2022
  ident: 2024.12.12.628150v1.50
  article-title: NEIL3 contributes to the Fanconi anemia/BRCA pathway by promoting the downstream double-strand break repair step
  publication-title: Cell Rep
– volume: 14
  start-page: 2995
  year: 2023
  ident: 2024.12.12.628150v1.68
  article-title: ExpressAnalyst: A unified platform for RNA-sequencing analysis in non-model species
  publication-title: Nat Commun
– year: 2011
  ident: 2024.12.12.628150v1.18
  article-title: Exosomes: Immune properties and potential clinical implementations
  publication-title: Semin Immunopathol
  doi: 10.1007/s00281-010-0233-9
– volume: 232
  start-page: 199
  year: 2014
  end-page: 209
  ident: 2024.12.12.628150v1.1
  article-title: Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours
  publication-title: J Pathol
– volume: 186
  start-page: 5603
  year: 2011
  end-page: 5611
  ident: 2024.12.12.628150v1.34
  article-title: Plexin-D1 Is a Novel Regulator of Germinal Centers and Humoral Immune Responses
  publication-title: The Journal of Immunology
– volume: 43
  start-page: W566
  year: 2015
  end-page: W570
  ident: 2024.12.12.628150v1.71
  article-title: ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap
  publication-title: Nucleic Acids Res
– volume: 6
  start-page: 1
  year: 2017
  end-page: 11
  ident: 2024.12.12.628150v1.12
  article-title: B cells and the humoral response in melanoma: The overlooked players of the tumor microenvironment
  publication-title: Oncoimmunology
– year: 2009
  ident: 2024.12.12.628150v1.4
  article-title: In Vivo Sensitized and In Vitro Activated B Cells Mediate Tumor Regression in Cancer Adoptive Immunotherapy
  publication-title: The Journal of Immunology
  doi: 10.4049/jimmunol.0803773
– volume: 12
  start-page: 1
  year: 2020
  end-page: 23
  ident: 2024.12.12.628150v1.26
  publication-title: Extracellular vesicles orchestrate immune and tumor interaction networks Cancers (Basel)
– volume: 12
  issue: 2301706
  year: 2023
  ident: 2024.12.12.628150v1.29
  article-title: Assessing Extracellular Vesicles in Human Biofluids Using Flow-Based Analyzers
  publication-title: Adv Healthc Mater
– volume: 560
  start-page: 382
  year: 2018
  end-page: 386
  ident: 2024.12.12.628150v1.14
  article-title: Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response
  publication-title: Nature
– volume: 9
  start-page: 785
  year: 2009
  end-page: 797
  ident: 2024.12.12.628150v1.43
  article-title: Emerging roles of E2Fs in cancer: an exit from cell cycle control
  publication-title: Nat Rev Cancer
– volume: 51
  start-page: 768
  year: 2005
  end-page: 775
  ident: 2024.12.12.628150v1.25
  article-title: Analysis of T-Cell Receptor Vβ Gene Repertoires after Immune Stimulation and in Malignancy by Use of Padlock Probes and Microarrays
  publication-title: Clin Chem
– volume: 12
  start-page: 1
  issue: 1
  year: 2022
  end-page: 10
  ident: 2024.12.12.628150v1.61
  article-title: Pan-cancer analysis based on epigenetic modification explains the value of HJURP in the tumor microenvironment
  publication-title: Scientific Reports
– volume: 1
  start-page: e37
  year: 2022
  ident: 2024.12.12.628150v1.28
  article-title: Serum extracellular vesicles profiling is associated with COVID-19 progression and immune responses
  publication-title: Journal of Extracellular Biology
– ident: 2024.12.12.628150v1.62
  publication-title: Lymphocytes Secrete Antigen-presentingVesicles
– volume: 48
  start-page: W244
  year: 2020
  end-page: W251
  ident: 2024.12.12.628150v1.67
  article-title: miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology
  publication-title: Nucleic Acids Res
– volume: 18
  start-page: 99
  year: 2008
  end-page: 113
  ident: 2024.12.12.628150v1.51
  article-title: Homologous recombination in DNA repair and DNA damage tolerance
  publication-title: Cell Res
– volume: 47
  start-page: W234
  year: 2019
  end-page: W241
  ident: 2024.12.12.628150v1.70
  article-title: NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis
  publication-title: Nucleic Acids Res
– volume: 38
  start-page: 1821
  year: 2010
  end-page: 1831
  ident: 2024.12.12.628150v1.53
  article-title: Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks
  publication-title: Nucleic Acids Res
– volume: 577
  year: 2020
  ident: 2024.12.12.628150v1.10
  article-title: Tertiary lymphoid structures improve immunotherapy and survival in melanoma
  publication-title: Nature
  doi: 10.1038/s41586-019-1914-8
– volume: 9
  start-page: e100328
  year: 2014
  ident: 2024.12.12.628150v1.58
  article-title: High Levels of SOX5 Decrease Proliferative Capacity of Human B Cells, but Permit Plasmablast Differentiation
  publication-title: PLoS One
– volume: 8
  start-page: 1
  issue: 1
  year: 2018
  end-page: 12
  ident: 2024.12.12.628150v1.33
  article-title: MiR-99b-5p and miR-203a-3p Function as Tumor Suppressors by Targeting IGF-1R in Gastric Cancer
  publication-title: Scientific Reports
– volume: 207
  start-page: 3004
  year: 2021
  end-page: 3015
  ident: 2024.12.12.628150v1.63
  article-title: CD24 and IgM Stimulation of B Cells Triggers Transfer of Functional B Cell Receptor to B Cell Recipients Via Extracellular Vesicles
  publication-title: The Journal of Immunology
– volume: 177
  start-page: 414
  year: 2019
  end-page: 427
  ident: 2024.12.12.628150v1.15
  article-title: Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory
  publication-title: Cell
– volume: 185
  start-page: 4977
  year: 2010
  end-page: 4982
  ident: 2024.12.12.628150v1.6
  article-title: CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes
  publication-title: The Journal of Immunology
– volume: 16
  start-page: 169
  year: 2015
  ident: 2024.12.12.628150v1.72
  article-title: InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams
  publication-title: BMC Bioinformatics
– volume: 577
  start-page: 549
  issue: 7791
  year: 2020
  end-page: 555
  ident: 2024.12.12.628150v1.11
  article-title: B cells and tertiary lymphoid structures promote immunotherapy response
  publication-title: Nature
– volume: 406
  start-page: 309
  year: 2000
  end-page: 314
  ident: 2024.12.12.628150v1.39
  article-title: A chemokine-driven positive feedback loop organizes lymphoid follicles
  publication-title: Nature
– volume: 8
  start-page: e3141
  issue: 10
  year: 2017
  end-page: e3141
  ident: 2024.12.12.628150v1.42
  article-title: miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer
  publication-title: Cell Death & Disease
– volume: 6
  year: 2021
  ident: 2024.12.12.628150v1.38
  article-title: Pax5 regulates B cell immunity by promoting PI3K signaling via PTEN down-regulation
  publication-title: Sci Immunol
  doi: 10.1126/sciimmunol.abg5003
– volume: 14
  year: 2023
  ident: 2024.12.12.628150v1.27
  article-title: Investigating the tumor-immune microenvironment through extracellular vesicles from frozen patient biopsies and 3D cultures
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2023.1176175
– volume: 18
  issue: 146
  year: 2019
  ident: 2024.12.12.628150v1.16
  article-title: The role of exosomal PD-L1 in tumor progression and immunotherapy
  publication-title: Mol Cancer
– volume: 109
  start-page: 2189
  issue: 8
  year: 2013
  end-page: 2198
  ident: 2024.12.12.628150v1.41
  article-title: MicroRNA-100/99a, deregulated in acute lymphoblastic leukaemia, suppress proliferation and promote apoptosis by regulating the FKBP51 and IGF1R/mTOR signalling pathways
  publication-title: British Journal of Cancer
– volume: 3
  start-page: e97
  issue: 4
  year: 2014
  end-page: e97
  ident: 2024.12.12.628150v1.30
  article-title: MiRNA-99a directly regulates AGO2 through translational repression in hepatocellular carcinoma
  publication-title: Oncogenesis
– volume: 197
  start-page: 44
  year: 1997
  end-page: 54
  ident: 2024.12.12.628150v1.24
  article-title: In staphylococcus enterotoxin B (SEB)-stimulated human PBMC, the LAK activity of non-T cells might have a major role in the mechanism of glomerular endothelial cells’ injury
  publication-title: Immunobiology
– volume: 19
  start-page: 2828
  year: 2000
  end-page: 2835
  ident: 2024.12.12.628150v1.46
  article-title: Cyclin E induction by genotoxic stress leads to apoptosis of hematopoietic cells
  publication-title: Oncogene
– volume: 43
  start-page: 804
  issue: 11
  year: 2024
  end-page: 820
  ident: 2024.12.12.628150v1.57
  article-title: HJURP is recruited to double-strand break sites and facilitates DNA repair by promoting chromatin reorganization
  publication-title: Oncogene
– volume: 6
  issue: 29736
  year: 2016
  ident: 2024.12.12.628150v1.59
  article-title: IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin
  publication-title: Sci Rep
– volume: 1839
  start-page: 1316
  year: 2014
  ident: 2024.12.12.628150v1.54
  article-title: FOXM1: An emerging master regulator of DNA damage response and genotoxic agent resistance
  publication-title: Biochim Biophys Acta
– volume: 5
  year: 2022
  ident: 2024.12.12.628150v1.66
  article-title: Live slow-frozen human tumor tissues viable for 2D, 3D, ex vivo cultures and single-cell RNAseq
  publication-title: Commun Biol
  doi: 10.1038/S42003-022-04025-0
– volume: 14
  start-page: 1
  issue: 1
  year: 2024
  end-page: 16
  ident: 2024.12.12.628150v1.64
  article-title: B cells secrete functional antigen-specific IgG antibodies on extracellular vesicles
  publication-title: Scientific Reports
– volume: 45
  start-page: W98
  year: 2017
  end-page: W102
  ident: 2024.12.12.628150v1.73
  article-title: GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses
  publication-title: Nucleic Acids Res
– volume: 12
  start-page: 631
  year: 2012
  end-page: 639
  ident: 2024.12.12.628150v1.44
  article-title: The Role of Cdc25A in the Regulation of Cell Proliferation and Apoptosis
  publication-title: Anticancer Agents Med Chem
– volume: 214
  start-page: 895
  year: 2017
  end-page: 904
  ident: 2024.12.12.628150v1.17
  article-title: PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity
  publication-title: Journal of Experimental Medicine
– volume: 13
  year: 2022
  ident: 2024.12.12.628150v1.19
  article-title: Innate immune checkpoint inhibitor resistance is associated with melanoma sub-types exhibiting invasive and de-differentiated gene expression signatures
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2022.955063
SSID ssj0002961374
Score 1.7478232
SecondaryResourceType preprint
Snippet The immune tumor microenvironment (TME) is increasingly recognized as a dynamic ecosystem where B cells play pivotal roles in modulating therapeutic responses,...
SourceID biorxiv
SourceType Open Access Repository
SubjectTerms Cancer Biology
Title B-Cells Extracellular Vesicles Shape Melanoma Response to Immune Checkpoint Therapy
URI https://www.biorxiv.org/content/10.1101/2024.12.12.628150
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1LawIxEA5FKfTWJ31KCr1uMTHZba6KYguKqC3eJMlOUGp3l3Vb7L9vZncpHnoo5BBCQmDy-GYmX2YIeXBW6I7p6MBJ_JIDygSGgfK1mIGTEcgyiOtoHA5fxctCLvZSfSGt0qzTfLf-Kt_xkbDtb9_qcLcZ2uoC_Xe-hPyptNabfotJzNowWDz-ule48jgVifod88-RXuOtZ9pDlMExaU50BvkJOYDklBxWKSG_z8isG_Rgs9nS_q7INbrVkSdK32Bb8tfobOWH0RFsdJJ-aDqtKK5Ai5Q-41cPoL0V2PcsXScFnVchA87JfNCf94ZBnfggMFHYDqw3icByq61DA8GDC_DY8dhILgA4d9Iap6PI6ybS2oiBVlIpo0RoGbdewbogjSRN4JLQGOODhZoJy52IY6sAwHWU8LgdxR7cr8h9LYNlVkW3WKKcloxjqeR0_Y8-N-QI25DnwcJb0ijyT7jzaF2YFml2--PJtFWuzw_3fpEd
linkProvider Cold Spring Harbor Laboratory Press
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3PS8MwFA66IXrzJ_42gteOJUsac3VsbLoNcVV2K0n6gsPZjq7K_O9N2iIePAg5FJIQeEn6vfflywtCN9Yw1dEdFVjur-SA1IEmIN1XQsByAbxM4jqehINndj_js5pwW9WySj3P8vX8szzH94Jt9_etNneb-Fidef7OlZDeOm-m5WnqTdR064x5SVd_1vrhWKh0YCVYfZj5Z3fn9tbD_YKV_i5qPqol5HtoA9J9tFW9C_l1gKZ3QRcWixXurYtceW7di0XxC6xKERuevrpueAwLlWbvCj9VOlfARYaH_r4H4O4rmLdlNk8LHFV5Aw5R1O9F3UFQv34QaBG2A-PiIjDUKGN9lOAQBmhiaaI5ZQCUWm60VUI4B4UbIwgoyaXUkoWGUOO8rCPUSLMUjhFOfJKwUBFmqGVJYiQA2I5kDrxF4hD-BF3XNoiXVYqL2NspJtSXyk6n_2hzhbYH0XgUj4aThzO04-u98IOE56hR5B9w4eC70JflHH0DMT6UWg
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1bS8MwFA66ofjmFe9G8LVjyZLWvDpX5mVjuCl7K0l6woazLV2V-e9N2iJ78EHIQyBNAydpv3P5zglCN0Yz2VEd6RnuUnJAKE8RELYXEzA8AF4WcR0M_f4re5zy6VoujKNVqnmar-ZfZRzfEbbt37f6uNvE2erM-e9s8-mt1WZazk3dymKziZr2rDF3ssNp69fPQoUFrIDVAc0_X2FV33rJNWgJd1FzJDPI99AGJPtoq7ob8vsAje-8LiwWS9xbFbl0_nVHGMVvsCyJbHg8s9PwABYyST8kfqm4roCLFD-4nA_A3Rno9yydJwWeVLUDDtEk7E26fa--AcFTgd_2tLWNQFMttXGWgkUZoLGhseKUAVBquFZGBoFVUrjWAQEpuBBKMF8Tqq2mdYQaSZrAMcKxKxTmS8I0NSyOtQAA0xHMAngQW5Q_Qde1DKKsKnMROTlFhLpWyen0H89coe3RfRg9PwyfztCOG3bcD-Kfo0aRf8KFRfBCXZZb9AOFvZVr
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=B-Cells+Extracellular+Vesicles+Shape+Melanoma+Response+to+Immune+Checkpoint+Therapy&rft.jtitle=bioRxiv&rft.au=Al+Hrout%2C+Ala%E2%80%99a&rft.au=Balayev%2C+Agshin&rft.au=Cervantes-Gracia%2C+Karla&rft.au=Gkelis%2C+Konstantinos&rft.date=2024-12-16&rft.pub=Cold+Spring+Harbor+Laboratory&rft.eissn=2692-8205&rft_id=info:doi/10.1101%2F2024.12.12.628150&rft.externalDocID=2024.12.12.628150v1