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The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer

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Abstract

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell death protein 1 (PD-1) antibody (nivolumab) in patients with gastric cancer.

Methods

We collected peripheral blood samples from gastric cancer patients (n = 29) before and after treatment with nivolumab and investigated the relationship between the frequency of surface or intracellular markers among nivolumab-binding PD-1+CD8+ T cells and treatment responses using multicolor flow cytometry. The tumors, lymph nodes, and peripheral blood of gastric cancer patients who underwent gastrectomy following nivolumab treatment were collected, and nivolumab-binding PD-1+CD8+ T cells in these tissue samples were characterized.

Results

Patients with a high frequency of CD103 among PD-1+CD8+ T cells in peripheral blood 2 weeks after the start of treatment had significantly better progression-free survival than the low group (P = 0.032). This CD103+PD-1+CD8+ T cell population mainly consisted of central memory T cells, showing the high expression of Ki-67 and few cytotoxic granules. In contrast, effector memory T cells were more frequently observed among CD103+PD-1+CD8+ T cells in tumors, which implied a change in the differentiated status of central memory T cells in lymph nodes and peripheral blood to effector memory T cells in tumors during the treatment with ICIs.

Conclusions

A high frequency of CD103 among PD-1+CD8+ T cells 2 weeks after nivolumab treatment in patients with advanced gastric cancer may be a useful biomarker for predicting the efficacy of anti-PD-1 therapy.

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Acknowledgements

We thank all the patients who contributed to this study. We thank M. Matsumoto and K. Goto for their help.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Yohei Nose, Takuro Saito, Kei Yamamoto, Atsunari Kawashima, Miya Haruna, Michinari Hirata, Azumi Ueyama, Kota Iwahori & Hisashi Wada

  2. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan

    Yohei Nose, Takuro Saito, Kei Yamamoto, Kotaro Yamashita, Koji Tanaka, Kazuyoshi Yamamoto, Tomoki Makino, Tsuyoshi Takahashi, Taroh Satoh, Yukinori Kurokawa, Hidetoshi Eguchi, Yuichiro Doki & Hisashi Wada

  3. Department of Urology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Atsunari Kawashima

  4. Laboratory for Innovative Therapy Research, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan

    Miya Haruna, Michinari Hirata & Azumi Ueyama

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  1. Yohei Nose
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  2. Takuro Saito
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Contributions

YN, TS, and HW contributed to the conception or design of the work. YN, TS, and KY performed the experiments. MH and AU helped perform the experiments. YN, TS, YD, and HW collected data and all authors analyzed data. YN drafted the article. TS, YD, and HW helped finalize the article. All authors have read and approved the final article. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.

Corresponding author

Correspondence to Takuro Saito.

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The authors have no relevant financial or non-financial interests to disclose.

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All procedures were in accordance with the Helsinki Declaration. The Human Ethics Review Committee of Osaka University Graduate School of Medicine approved the protocol for this study.

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Informed consent was obtained from all individual participants included in the study.

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Nose, Y., Saito, T., Yamamoto, K. et al. The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer. Cancer Immunol Immunother 72, 169–181 (2023). https://doi.org/10.1007/s00262-022-03240-2

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