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. 2024 Mar;27(2):248-262.
doi: 10.1007/s10120-023-01456-4. Epub 2024 Jan 13.

Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer

Chikanori Tsutsumi  1 , Kenoki Ohuchida  2   3 , Naoki Katayama  1 , Yutaka Yamada  4 , Shoichi Nakamura  1 , Sho Okuda  1 , Yoshiki Otsubo  1 , Chika Iwamoto  1 , Nobuhiro Torata  1 , Kohei Horioka  1 , Koji Shindo  1 , Yusuke Mizuuchi  1 , Naoki Ikenaga  1 , Kohei Nakata  1 , Eishi Nagai  1 , Takashi Morisaki  5 , Yoshinao Oda  4 , Masafumi Nakamura  1
Affiliations

Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer

Chikanori Tsutsumi et al. Gastric Cancer. 2024 Mar.

Abstract

Background: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME.

Methods: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients.

Results: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3- M-MDSCs and were abundant in treatment-resistant GC patients.

Conclusions: The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.

Keywords: Gastric cancer; Immediate early response 3; Monocytic myeloid-derived suppressor cells; Tumor immune microenvironment.

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References

    1. Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandalà M, Ryu MH, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392:123–33. - DOI - PubMed
    1. Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71. https://doi.org/10.1016/S0140-6736(17)31827-5 . - DOI - PubMed
    1. Eum HH, Kwon M, Ryu D, Jo A, Chung W, Kim N, et al. Tumor-promoting macrophages prevail in malignant ascites of advanced gastric cancer. Exp Mol Med. 2020;52:1976–88. https://doi.org/10.1038/s12276-020-00538-y . - DOI - PubMed - PMC
    1. Sathe A, Grimes SM, Lau BT, Chen J, Suarez C, Huang RJ, Poultsides GJH. Single-cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment. Clin Cancer Res. 2020;26:2640–53. - DOI - PubMed - PMC
    1. Fu K, Hui B, Wang Q, Lu C, Shi W, Zhang Z, et al. Single-cell RNA sequencing of immune cells in gastric cancer patients. Aging. 2020;12:2747–63. - DOI - PubMed - PMC