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Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer

BACKGROUND: Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103(+)CD8(+) tumor-inf...

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Autores principales: Natsuki, Seiji, Tanaka, Hiroaki, Nishiyama, Masaki, Deguchi, Sota, Miki, Yuichiro, Yoshii, Mami, Tamura, Tatsuro, Toyokawa, Takahiro, Lee, Shigeru, Maeda, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588150/
https://www.ncbi.nlm.nih.gov/pubmed/37864146
http://dx.doi.org/10.1186/s12885-023-11438-5
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author Natsuki, Seiji
Tanaka, Hiroaki
Nishiyama, Masaki
Deguchi, Sota
Miki, Yuichiro
Yoshii, Mami
Tamura, Tatsuro
Toyokawa, Takahiro
Lee, Shigeru
Maeda, Kiyoshi
author_facet Natsuki, Seiji
Tanaka, Hiroaki
Nishiyama, Masaki
Deguchi, Sota
Miki, Yuichiro
Yoshii, Mami
Tamura, Tatsuro
Toyokawa, Takahiro
Lee, Shigeru
Maeda, Kiyoshi
author_sort Natsuki, Seiji
collection PubMed
description BACKGROUND: Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103(+)CD8(+) tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (T(RM)), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and T(RM). METHODS: The relationships between T(RM) infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, T(RM) infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness. RESULTS: T(RM)-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than T(RM)-poor patients (6 vs 2 patients). T(RM) infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but T(RM) may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with T(RM) but did not impact prognosis. CONCLUSIONS: T(RM)-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that T(RM) are vital for antitumor immunity and are a promising predictor of ICIs effectiveness. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11438-5.
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spelling pubmed-105881502023-10-21 Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer Natsuki, Seiji Tanaka, Hiroaki Nishiyama, Masaki Deguchi, Sota Miki, Yuichiro Yoshii, Mami Tamura, Tatsuro Toyokawa, Takahiro Lee, Shigeru Maeda, Kiyoshi BMC Cancer Research BACKGROUND: Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103(+)CD8(+) tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (T(RM)), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and T(RM). METHODS: The relationships between T(RM) infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, T(RM) infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness. RESULTS: T(RM)-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than T(RM)-poor patients (6 vs 2 patients). T(RM) infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but T(RM) may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with T(RM) but did not impact prognosis. CONCLUSIONS: T(RM)-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that T(RM) are vital for antitumor immunity and are a promising predictor of ICIs effectiveness. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11438-5. BioMed Central 2023-10-20 /pmc/articles/PMC10588150/ /pubmed/37864146 http://dx.doi.org/10.1186/s12885-023-11438-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Natsuki, Seiji
Tanaka, Hiroaki
Nishiyama, Masaki
Deguchi, Sota
Miki, Yuichiro
Yoshii, Mami
Tamura, Tatsuro
Toyokawa, Takahiro
Lee, Shigeru
Maeda, Kiyoshi
Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
title Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
title_full Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
title_fullStr Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
title_full_unstemmed Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
title_short Significance of CD103(+) tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
title_sort significance of cd103(+) tissue-resident memory t cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588150/
https://www.ncbi.nlm.nih.gov/pubmed/37864146
http://dx.doi.org/10.1186/s12885-023-11438-5
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