Variable indoleamine 2,3‐dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy
Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high e...
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| Published in | Cancer science Vol. 110; no. 11; pp. 3434 - 3441 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
John Wiley & Sons, Inc
01.11.2019
John Wiley and Sons Inc |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1347-9032 1349-7006 1349-7006 |
| DOI | 10.1111/cas.14195 |
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| Abstract | Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3‐dioxygenase (IDO) is correlated to a response to anti–CTLA‐4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti–PD‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD‐L1 expression with response to anti–PD‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–PD‐1 antibody from the perspective of IDO and PD‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression‐free survival (HR = 0.33, 95% CI = 0.13‐0.81, P = 0.016), whereas PD‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of IDO in tumors was found in non–responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.
Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. |
|---|---|
| AbstractList | Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (
PD
‐L1) is a well‐studied biomarker for response to anti–programmed death‐1
PD
‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3‐dioxygenase (
IDO
) is correlated to a response to anti–
CTLA
‐4 treatment in melanoma. However, it is still unknown whether the
IDO
expression is associated with response to anti–
PD
‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of
IDO
and
PD
‐L1 expression with response to anti–
PD
‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–
PD
‐1 antibody from the perspective of
IDO
and
PD
‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of
IDO
in tumors was associated with poor progression‐free survival (
HR
= 0.33, 95%
CI
= 0.13‐0.81,
P
=
0.016), whereas
PD
‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of
IDO
in tumors was found in non–responders compared to responders. Assessment of the
IDO
expression could be useful for the identification of suitable candidates for anti–
PD
‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings. Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3‐dioxygenase (IDO) is correlated to a response to anti–CTLA‐4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti–PD‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD‐L1 expression with response to anti–PD‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–PD‐1 antibody from the perspective of IDO and PD‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression‐free survival (HR = 0.33, 95% CI = 0.13‐0.81, P = 0.016), whereas PD‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of IDO in tumors was found in non–responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3‐dioxygenase (IDO) is correlated to a response to anti–CTLA‐4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti–PD‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD‐L1 expression with response to anti–PD‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–PD‐1 antibody from the perspective of IDO and PD‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression‐free survival (HR = 0.33, 95% CI = 0.13‐0.81, P = 0.016), whereas PD‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of IDO in tumors was found in non–responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings. Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings. Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3‐dioxygenase (IDO) is correlated to a response to anti–CTLA‐4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti–PD‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD‐L1 expression with response to anti–PD‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–PD‐1 antibody from the perspective of IDO and PD‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression‐free survival (HR = 0.33, 95% CI = 0.13‐0.81, P = 0.016), whereas PD‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of IDO in tumors was found in non–responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings. |
| Author | Fujimura, Taku Matsushita, Shigeto Otsuka, Atsushi Kataoka, Tatsuki R. Irie, Hiroyuki Hirata, Masahiro Ishida, Yoshihiro Hata, Hiroo Kabashima, Kenji Nakashima, Chisa Funakoshi, Takeru Yamamoto, Yuki Fujisawa, Yasuhiro Iga, Natsuko Yoshino, Koji Uchi, Hiroshi |
| AuthorAffiliation | 6 Department of Dermatology Wakayama Medical University Wakayama Japan 7 Department of Dermatology Keio University School of Medicine Tokyo Japan 8 Department of Dermatology University of Tsukuba Tsukuba Japan 10 Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan 11 Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan 4 Department of Dermato‐Oncology/Dermatology National Hospital Organization Kagoshima Medical Center Kagoshima Japan 3 Department of Diagnostic Pathology Kyoto University Graduate School of Medicine Kyoto Japan 2 Translational Research Department for Skin and Brain Diseases Kyoto University Graduate School of Medicine Kyoto Japan 5 Department of Dermatology Kyusyu University Graduate School of Medicine Fukuoka Japan 12 Singapore Immunology Network (SIgN) and Skin Research Institute of Singapore (SRIS) Agency for Science, Technology and Research (ASTAR) Singapore Singapore 9 Department of Dermatology Tokyo Metropol |
| AuthorAffiliation_xml | – name: 11 Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan – name: 12 Singapore Immunology Network (SIgN) and Skin Research Institute of Singapore (SRIS) Agency for Science, Technology and Research (ASTAR) Singapore Singapore – name: 10 Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan – name: 3 Department of Diagnostic Pathology Kyoto University Graduate School of Medicine Kyoto Japan – name: 1 Department of Dermatology Kyoto University Graduate School of Medicine Kyoto Japan – name: 7 Department of Dermatology Keio University School of Medicine Tokyo Japan – name: 5 Department of Dermatology Kyusyu University Graduate School of Medicine Fukuoka Japan – name: 6 Department of Dermatology Wakayama Medical University Wakayama Japan – name: 2 Translational Research Department for Skin and Brain Diseases Kyoto University Graduate School of Medicine Kyoto Japan – name: 8 Department of Dermatology University of Tsukuba Tsukuba Japan – name: 4 Department of Dermato‐Oncology/Dermatology National Hospital Organization Kagoshima Medical Center Kagoshima Japan – name: 9 Department of Dermatology Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan |
| Author_xml | – sequence: 1 givenname: Natsuko orcidid: 0000-0001-7799-8110 surname: Iga fullname: Iga, Natsuko organization: Kyoto University Graduate School of Medicine – sequence: 2 givenname: Atsushi surname: Otsuka fullname: Otsuka, Atsushi email: otsukamn@kuhp.kyoto-u.ac.jp organization: Kyoto University Graduate School of Medicine – sequence: 3 givenname: Masahiro orcidid: 0000-0001-9211-0511 surname: Hirata fullname: Hirata, Masahiro organization: Kyoto University Graduate School of Medicine – sequence: 4 givenname: Tatsuki R. orcidid: 0000-0003-3095-8976 surname: Kataoka fullname: Kataoka, Tatsuki R. organization: Kyoto University Graduate School of Medicine – sequence: 5 givenname: Hiroyuki surname: Irie fullname: Irie, Hiroyuki organization: Kyoto University Graduate School of Medicine – sequence: 6 givenname: Chisa surname: Nakashima fullname: Nakashima, Chisa organization: Kyoto University Graduate School of Medicine – sequence: 7 givenname: Shigeto surname: Matsushita fullname: Matsushita, Shigeto organization: National Hospital Organization Kagoshima Medical Center – sequence: 8 givenname: Hiroshi surname: Uchi fullname: Uchi, Hiroshi organization: Kyusyu University Graduate School of Medicine – sequence: 9 givenname: Yuki surname: Yamamoto fullname: Yamamoto, Yuki organization: Wakayama Medical University – sequence: 10 givenname: Takeru surname: Funakoshi fullname: Funakoshi, Takeru organization: Keio University School of Medicine – sequence: 11 givenname: Yasuhiro surname: Fujisawa fullname: Fujisawa, Yasuhiro organization: University of Tsukuba – sequence: 12 givenname: Koji surname: Yoshino fullname: Yoshino, Koji organization: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital – sequence: 13 givenname: Taku orcidid: 0000-0001-6809-5833 surname: Fujimura fullname: Fujimura, Taku organization: Tohoku University Graduate School of Medicine – sequence: 14 givenname: Hiroo surname: Hata fullname: Hata, Hiroo organization: Hokkaido University Graduate School of Medicine – sequence: 15 givenname: Yoshihiro surname: Ishida fullname: Ishida, Yoshihiro organization: Kyoto University Graduate School of Medicine – sequence: 16 givenname: Kenji surname: Kabashima fullname: Kabashima, Kenji organization: Agency for Science, Technology and Research (ASTAR) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31509303$$D View this record in MEDLINE/PubMed |
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| Copyright | 2019 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. 2019. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Title | Variable indoleamine 2,3‐dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy |
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