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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1497004
This article is part of the Research Topic Community Series in Implications of Immune Landscape in Tumor Microenvironment: Volume II View all articles

Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer Author

Provisionally accepted
Ning Zhang Ning Zhang 1Chunyu Li Chunyu Li 1Zehua Zhao Zehua Zhao 1Wentao Wang Wentao Wang 2Biying Jiang Biying Jiang 1Fujing Sun Fujing Sun 1Yong Zhang Yong Zhang 1*Yanmei Zhu Yanmei Zhu 1*
  • 1 Departments of Pathology, Liaoning Cancer Hospital, China Medical University, Shenyang, China
  • 2 Department of Gastrointestinal Cancer, Liaoning Cancer Hospital, Shenyang, Liaoning Province, China

The final, formatted version of the article will be published soon.

    The therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.: The study included 128 patients with resectable stage II-III gastric cancer, in which 63 were given neoadjuvant Io+Chemo，and 65 Chemo alone. Patients given Io+Chemo were treated with 2-4 cycles of PD-(L)1 inhibitor (Pembrolizumab, Sintililimab or Nivolumab) with S-1 and oxaliplatin (SOX) or capecitabine and oxaliplatin (XELOX) before surgical resection. Patients given Chemo were treated with 2-4 cycles of SOX or XELOX before surgical resection. Tumor tissues were evaluated for tumor-infiltrating immune cells (TIICs) using immunohistochemistry and QuPath software quantitative analysis, for detecting T, B, NK, plasma cells, and macrophages. The relationship between TIICs and different neoadjuvant treatment regimens and pathological responses was also explored.Results: Compared with Chemo, Io+Chemo induced higher rates of pathological complete response (33.3 vs. 9.2%, p=0.001) and major pathological response (MPR) (49.2 vs. 30.8%, p=0.033). Compared with Chemo group, density of CD4 + (1904.8 vs. 1530), CD8 + (1982.9 vs. 1124.4), CD20 + (1115.6 vs. 574), CD38 + (1580.4 vs. 1128), CD138 + (1237.2 vs. 496.4), and CD56 + (596.8 vs. 159) cells was increased 24.5%, 76.4%, 94.4%, 40.1%, and 149.2% respectively, whereas CD163 + macrophages (994.4 vs. 1706) was decreased 41.7% in Io+Chemo group. 4 Conclusions: Our study favors neoadjuvant Io+Chemo over Chemo and reveals Io+Chemo can induce the formation of an immune-activated microenvironment that make Io+Chemo superior to Chemo.

    Keywords: gastric cancer, Tumor-infiltrating immune cells, Tumor immune microenvironment, Neoadjuvant Therapy, immunochemotherapy

    Received: 16 Sep 2024; Accepted: 10 Jan 2025.

    Copyright: © 2025 Zhang, Li, Zhao, Wang, Jiang, Sun, Zhang and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yong Zhang, Departments of Pathology, Liaoning Cancer Hospital, China Medical University, Shenyang, China
    Yanmei Zhu, Departments of Pathology, Liaoning Cancer Hospital, China Medical University, Shenyang, China

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