Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab

Abstract Anti-PD-L1 antibodies benefit many cancer patients, even those with “non-inflamed tumor”. Determining which patients will benefit remains an important clinical goal. In a non-inflamed tumor mouse model, we found that PD-L1 was highly expressed on antigen-presenting cells (APCs) especially o...

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Autores principales:	Toshiki Iwai, Masamichi Sugimoto, Namrata S. Patil, Daniel Bower, Miho Suzuki, Chie Kato, Keigo Yorozu, Mitsue Kurasawa, David S. Shames, Osamu Kondoh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b94adbd323b4bf69ee418f876c26582
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spelling	oai:doaj.org-article:4b94adbd323b4bf69ee418f876c265822021-12-02T15:39:41ZBoth T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab10.1038/s41598-021-93113-y2045-2322https://doaj.org/article/4b94adbd323b4bf69ee418f876c265822021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93113-yhttps://doaj.org/toc/2045-2322Abstract Anti-PD-L1 antibodies benefit many cancer patients, even those with “non-inflamed tumor”. Determining which patients will benefit remains an important clinical goal. In a non-inflamed tumor mouse model, we found that PD-L1 was highly expressed on antigen-presenting cells (APCs) especially on CD103+ CD11c+ dendritic cells in tumor-draining lymph nodes (dLNs), suppressing T-cell priming by APCs. In this model, anti-PD-L1 antibodies enhanced T-cell priming and increased CXCR3+ activated T-cells in dLNs, which was followed by the trafficking of T-cells to tumors in response to CXCR3 ligands. As predictive biomarker, each APCs-related gene expression (AP score) alone or T-cells trafficking-related chemokine gene expression (T score) alone were still less than perfect among the 17 mouse models examined. However a combining score of AP score and T score (AP/T score) precisely identified anti-PD-L1-sensitive tumors. In the phase 3 trial of atezolizumab vs docetaxel in advanced NSCLC patients (OAK), the AP/T score could identify atezolizumab-treated NSCLC patients who achieved significant improvement in overall survival. This biomarker concept would be a clinically valuable for prediction of anti-PD-L1 antibody efficacy.Toshiki IwaiMasamichi SugimotoNamrata S. PatilDaniel BowerMiho SuzukiChie KatoKeigo YorozuMitsue KurasawaDavid S. ShamesOsamu KondohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Toshiki Iwai Masamichi Sugimoto Namrata S. Patil Daniel Bower Miho Suzuki Chie Kato Keigo Yorozu Mitsue Kurasawa David S. Shames Osamu Kondoh Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab
description	Abstract Anti-PD-L1 antibodies benefit many cancer patients, even those with “non-inflamed tumor”. Determining which patients will benefit remains an important clinical goal. In a non-inflamed tumor mouse model, we found that PD-L1 was highly expressed on antigen-presenting cells (APCs) especially on CD103+ CD11c+ dendritic cells in tumor-draining lymph nodes (dLNs), suppressing T-cell priming by APCs. In this model, anti-PD-L1 antibodies enhanced T-cell priming and increased CXCR3+ activated T-cells in dLNs, which was followed by the trafficking of T-cells to tumors in response to CXCR3 ligands. As predictive biomarker, each APCs-related gene expression (AP score) alone or T-cells trafficking-related chemokine gene expression (T score) alone were still less than perfect among the 17 mouse models examined. However a combining score of AP score and T score (AP/T score) precisely identified anti-PD-L1-sensitive tumors. In the phase 3 trial of atezolizumab vs docetaxel in advanced NSCLC patients (OAK), the AP/T score could identify atezolizumab-treated NSCLC patients who achieved significant improvement in overall survival. This biomarker concept would be a clinically valuable for prediction of anti-PD-L1 antibody efficacy.
format	article
author	Toshiki Iwai Masamichi Sugimoto Namrata S. Patil Daniel Bower Miho Suzuki Chie Kato Keigo Yorozu Mitsue Kurasawa David S. Shames Osamu Kondoh
author_facet	Toshiki Iwai Masamichi Sugimoto Namrata S. Patil Daniel Bower Miho Suzuki Chie Kato Keigo Yorozu Mitsue Kurasawa David S. Shames Osamu Kondoh
author_sort	Toshiki Iwai
title	Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab
title_short	Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab
title_full	Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab
title_fullStr	Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab
title_full_unstemmed	Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab
title_sort	both t cell priming in lymph node and cxcr3-dependent migration are the key events for predicting the response of atezolizumab
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4b94adbd323b4bf69ee418f876c26582
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Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab

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