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13-01-2024 | Gastric Cancer | Original Article

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

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

Published in: Gastric Cancer | Issue 2/2024

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.

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Title: Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer
Authors: Chikanori Tsutsumi
Kenoki Ohuchida
Naoki Katayama
Yutaka Yamada
Shoichi Nakamura
Sho Okuda
Yoshiki Otsubo
Chika Iwamoto
Nobuhiro Torata
Kohei Horioka
Koji Shindo
Yusuke Mizuuchi
Naoki Ikenaga
Kohei Nakata
Eishi Nagai
Takashi Morisaki
Yoshinao Oda
Masafumi Nakamura
Publication date: 13-01-2024
Publisher: Springer Nature Singapore
Keywords: Gastric Cancer
Gastric Cancer
Published in: Gastric Cancer / Issue 2/2024
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI: https://doi.org/10.1007/s10120-023-01456-4

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