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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2020
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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. |
format | Online Article Text |
id | pubmed-7586238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
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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