Parallel profiling of immune infiltrate subsets in uveal melanoma versus cutaneous melanoma unveils similarities and differences: A pilot study

The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients...

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Published inOncoimmunology Vol. 6; no. 6; p. e1321187
Main Authors Qin, Yong, Petaccia de Macedo, Mariana, Reuben, Alexandre, Forget, Marie-Andrée, Haymaker, Cara, Bernatchez, Chantale, Spencer, Christine N., Gopalakrishnan, Vancheswaran, Reddy, Sujan, Cooper, Zachary A., Fulbright, Orenthial J., Ramachandran, Renjith, Wahl, Arely, Flores, Esteban, Thorsen, Shawne T., Tavera, Rene J., Conrad, Claudius, Williams, Michelle D., Tetzlaff, Michael T., Wang, Wei-Lien, Gombos, Dan S., Esmaeli, Bita, Amaria, Rodabe N., Hwu, Patrick, Wargo, Jennifer A., Lazar, Alexander J., Patel, Sapna P.
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 03.06.2017
Taylor & Francis Group
Subjects
Brief Report
Cutaneous melanoma
immune profile
tumor infiltrating lymphocytes
uveal melanoma
immune profile
Cutaneous melanoma
tumor infiltrating lymphocytes
uveal melanoma
Online AccessGet full text
ISSN2162-402X
2162-4011
2162-402X
DOI10.1080/2162402X.2017.1321187

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Abstract The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8 + T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
AbstractList The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8 + T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8 T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
Author Reuben, Alexandre
Haymaker, Cara
Hwu, Patrick
Patel, Sapna P.
Ramachandran, Renjith
Wahl, Arely
Thorsen, Shawne T.
Spencer, Christine N.
Cooper, Zachary A.
Wargo, Jennifer A.
Tavera, Rene J.
Williams, Michelle D.
Tetzlaff, Michael T.
Gombos, Dan S.
Flores, Esteban
Wang, Wei-Lien
Amaria, Rodabe N.
Bernatchez, Chantale
Qin, Yong
Reddy, Sujan
Fulbright, Orenthial J.
Petaccia de Macedo, Mariana
Gopalakrishnan, Vancheswaran
Forget, Marie-Andrée
Conrad, Claudius
Lazar, Alexander J.
Esmaeli, Bita
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ContentType Journal Article
Copyright 2017 The Author(s). Published with license by Taylor & Francis Group, LLC © Yong Qin, Mariana Petaccia de Macedo, Alexandre Reuben, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Christine N. Spencer, Vancheswaran Gopalakrishnan, Sujan Reddy, Zachary A. Cooper, Orenthial J. Fulbright, Renjith Ramachandran, Arely Wahl, Esteban Flores, Shawne T. Thorsen, Rene J. Tavera, Claudius Conrad, Michelle D. Williams, Michael T. Tetzlaff, Wei-Lien Wang, Dan S. Gombos, Bita Esmaeli, Rodabe N. Amaria, Patrick Hwu, Jennifer A. Wargo, Alexander J. Lazar, and Sapna P. Patel 2017
2017 The Author(s). Published with license by Taylor & Francis Group, LLC 2017 The Author(s)
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Issue 6
Keywords immune profile
Cutaneous melanoma
tumor infiltrating lymphocytes
uveal melanoma
Language English
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content type line 23
Now at MedImmune, Gaithersburg, MD 20878 USA.
These authors contributed equally to this manuscript.
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Snippet The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To...
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SubjectTerms Brief Report
Cutaneous melanoma
immune profile
tumor infiltrating lymphocytes
uveal melanoma
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Title Parallel profiling of immune infiltrate subsets in uveal melanoma versus cutaneous melanoma unveils similarities and differences: A pilot study
URI https://www.tandfonline.com/doi/abs/10.1080/2162402X.2017.1321187
https://www.ncbi.nlm.nih.gov/pubmed/28680759
https://www.proquest.com/docview/1916708863
https://pubmed.ncbi.nlm.nih.gov/PMC5486182
https://doaj.org/article/bc530e9b1b874349a93364fbb2c1eec1
Volume 6
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