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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 |
doi: 10.3389/fimmu.2025.1521278
This article is part of the Research Topic Gastric Cancer: Individualized Immunotherapeutic Approaches and Biomarker-Driven Strategies View all 7 articles
Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer
Provisionally accepted
Yasunobu Mano
1,2
Yuka Igarashi
1,2*
Keisuke Komori
3,4*
Itaru Hashimoto
3,4*
Hayato Watanabe
3*
Kosuke Takahashi
3*
Kazuki Kano
3*
Hirohito Fujikawa
3*
Takanobu Yamada
3
Hidetomo Himuro
1,2*
Taku Kouro
1,2
Feifei Wei
1,2
Kayoko Tsuji
1,2
Shun Horaguchi
1,2,5*
Mitsuru Komahashi
1,2,5*
Takashi Oshima
3*
Tetsuro Sasada
1,2*- 1 Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan
- 2 Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, Japan
- 3 Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
- 4 Department of Surgery, Yokohama City University, Yokohama, Japan
- 5 Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
The omentum is a common site of peritoneal metastasis in various cancers, including gastric cancer. It contains immune cell aggregates known as milky spots, which provide a microenvironment for peritoneal immunity by regulating innate and adaptive immune responses. In this study, we investigated gene expression profiles in cells from omental milky spots of patients with gastric cancer (n = 37) by RNA sequencing analysis and classified the patients into four groups (G1-4). Notably, significant differences were observed between the groups in terms of macroscopic type, lymphatic invasion, venous invasion, and pathological stage (pStage). G3, which was enriched in genes related to acquired immunity, showed earlier tumor stages (macroscopic type 0, Ly0, V0, and pStage I) and a better prognosis. In contrast, G4 showed enrichment of genes related to neutrophils and innate immunity; G1 and G2 showed no enrichment of innate or adaptive immune-related genes, suggesting an immune desert microenvironment. Cytometric analysis revealed significantly more T and B cells and fewer neutrophils in G3. Accordingly, the immune microenvironment in omental milky spots may vary depending on the stage of gastric cancer progression. When univariate Cox proportional hazards regression models were used to search for prognostically relevant genes specific to G3, 23 potential prognostic genes were identified as common genes associated with relapse-free survival and overall survival. In addition, the multivariate Cox proportional hazards model using these prognostic genes and clinicopathological information showed that combining the B cell marker CD19 and Ly had a high predictive accuracy for prognosis. Based on this study's results, it is possible that tumor progression, such as lymphatic and/or venous infiltration of tumor cells, may affect the immune cell composition and proportions in omental milky spots of patients with gastric cancer and analysis of gene expression in omental milky spots may help to predict gastric cancer prognosis.
Keywords: Omental milky spots, gastric cancer, Adaptive Immune Responses, Lymphatic invasion, immune microenvironment
Received: 01 Nov 2024; Accepted: 02 Jan 2025.
Copyright: © 2025 Mano, Igarashi, Komori, Hashimoto, Watanabe, Takahashi, Kano, Fujikawa, Yamada, Himuro, Kouro, Wei, Tsuji, Horaguchi, Komahashi, Oshima and Sasada. 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:
Yuka Igarashi, Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, 241-0815, Kanagawa, Japan
Keisuke Komori, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Itaru Hashimoto, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Hayato Watanabe, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Kosuke Takahashi, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Kazuki Kano, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Hirohito Fujikawa, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Hidetomo Himuro, Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, 241-0815, Kanagawa, Japan
Shun Horaguchi, Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, 241-0815, Kanagawa, Japan
Mitsuru Komahashi, Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, 241-0815, Kanagawa, Japan
Takashi Oshima, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
Tetsuro Sasada, Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, 241-0815, Kanagawa, Japan
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