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TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer

This study aimed to identify novel prognostic biomarker for advanced renal cell carcinoma (RCC) patients treated with anti-PD-1 therapy, using quantitative multi-immunofluorescence (IF) analysis of tumor immunity. Twenty-five consecutive patients who had metastatic or unresectable RCC treated with a...

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Autores principales: Kato, Renpei, Jinnouchi, Noriaki, Tuyukubo, Takashi, Ikarashi, Daiki, Matsuura, Tomohiko, Maekawa, Shigekatsu, Kato, Yoichiro, Kanehira, Mitsugu, Takata, Ryo, Ishida, Kazuyuki, Obara, Wataru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586238/
https://www.ncbi.nlm.nih.gov/pubmed/33129110
http://dx.doi.org/10.1016/j.tranon.2020.100918
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author Kato, Renpei
Jinnouchi, Noriaki
Tuyukubo, Takashi
Ikarashi, Daiki
Matsuura, Tomohiko
Maekawa, Shigekatsu
Kato, Yoichiro
Kanehira, Mitsugu
Takata, Ryo
Ishida, Kazuyuki
Obara, Wataru
author_facet Kato, Renpei
Jinnouchi, Noriaki
Tuyukubo, Takashi
Ikarashi, Daiki
Matsuura, Tomohiko
Maekawa, Shigekatsu
Kato, Yoichiro
Kanehira, Mitsugu
Takata, Ryo
Ishida, Kazuyuki
Obara, Wataru
author_sort Kato, Renpei
collection PubMed
description This study aimed to identify novel prognostic biomarker for advanced renal cell carcinoma (RCC) patients treated with anti-PD-1 therapy, using quantitative multi-immunofluorescence (IF) analysis of tumor immunity. Twenty-five consecutive patients who had metastatic or unresectable RCC treated with anti-PD-1 therapy were studied. The patients were divided into a responder group (n = 12) and a non-responder group (n = 13). Quantitative multi-IF staining was performed on biopsy or surgical kidney samples using a panel of antibodies. Sections were scanned using a Mantra microscope, and the images were analyzed with inForm™ software. Responders had significantly higher rate of TIM3-positive tumor (100% versus 53.9%, p < 0.01) than non-responders. Multi-IF analysis showed that TIM3 expression on tumor cells was most strongly related to response to anti-PD-1 therapy, while some of the known immune-related prognostic factors in RCC (CD45RO, FOXP3, VEGF, PD-L1, PD-L2, CD163) had no significant association. Patients with TIM3-positive tumor showed significantly longer overall survival (not reached median time versus 6.0 months, p < 0.01) and progression-free survival (18.9 versus 1.1 months, p < 0.01) than those with TIM3-negative tumor. Immunohistochemistry study using samples obtained after anti-PD-1 therapy showed infiltration of CD163 macrophages and release of HMGB1, a ligand of TIM3, in necrotic tumor area. In conclusion, our study found clinical correlation between TIM3 expression on tumor cells and response to anti-PD-1 therapy. Further studies are warranted to verify whether TIM3 expression on tumor cells before systemic therapy predicts the efficacy of anti-PD-1 therapy for RCC in the clinical setting.
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spelling pubmed-75862382020-10-30 TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer Kato, Renpei Jinnouchi, Noriaki Tuyukubo, Takashi Ikarashi, Daiki Matsuura, Tomohiko Maekawa, Shigekatsu Kato, Yoichiro Kanehira, Mitsugu Takata, Ryo Ishida, Kazuyuki Obara, Wataru Transl Oncol Original article This study aimed to identify novel prognostic biomarker for advanced renal cell carcinoma (RCC) patients treated with anti-PD-1 therapy, using quantitative multi-immunofluorescence (IF) analysis of tumor immunity. Twenty-five consecutive patients who had metastatic or unresectable RCC treated with anti-PD-1 therapy were studied. The patients were divided into a responder group (n = 12) and a non-responder group (n = 13). Quantitative multi-IF staining was performed on biopsy or surgical kidney samples using a panel of antibodies. Sections were scanned using a Mantra microscope, and the images were analyzed with inForm™ software. Responders had significantly higher rate of TIM3-positive tumor (100% versus 53.9%, p < 0.01) than non-responders. Multi-IF analysis showed that TIM3 expression on tumor cells was most strongly related to response to anti-PD-1 therapy, while some of the known immune-related prognostic factors in RCC (CD45RO, FOXP3, VEGF, PD-L1, PD-L2, CD163) had no significant association. Patients with TIM3-positive tumor showed significantly longer overall survival (not reached median time versus 6.0 months, p < 0.01) and progression-free survival (18.9 versus 1.1 months, p < 0.01) than those with TIM3-negative tumor. Immunohistochemistry study using samples obtained after anti-PD-1 therapy showed infiltration of CD163 macrophages and release of HMGB1, a ligand of TIM3, in necrotic tumor area. In conclusion, our study found clinical correlation between TIM3 expression on tumor cells and response to anti-PD-1 therapy. Further studies are warranted to verify whether TIM3 expression on tumor cells before systemic therapy predicts the efficacy of anti-PD-1 therapy for RCC in the clinical setting. Neoplasia Press 2020-10-22 /pmc/articles/PMC7586238/ /pubmed/33129110 http://dx.doi.org/10.1016/j.tranon.2020.100918 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Kato, Renpei
Jinnouchi, Noriaki
Tuyukubo, Takashi
Ikarashi, Daiki
Matsuura, Tomohiko
Maekawa, Shigekatsu
Kato, Yoichiro
Kanehira, Mitsugu
Takata, Ryo
Ishida, Kazuyuki
Obara, Wataru
TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer
title TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer
title_full TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer
title_fullStr TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer
title_full_unstemmed TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer
title_short TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer
title_sort tim3 expression on tumor cells predicts response to anti-pd-1 therapy for renal cancer
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586238/
https://www.ncbi.nlm.nih.gov/pubmed/33129110
http://dx.doi.org/10.1016/j.tranon.2020.100918
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