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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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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. |
format | Online Article Text |
id | pubmed-10588150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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