Editorial
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Sep 24, 2024; 15(9): 1126-1131
Published online Sep 24, 2024. doi: 10.5306/wjco.v15.i9.1126
Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma
Yu-Qiong Xie, Chun-Chun Li, Mei-Rong Yu, Jiang Cao
Yu-Qiong Xie, Chun-Chun Li, Mei-Rong Yu, Jiang Cao, Center for Basic and Translational Research, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
Author contributions: Cao J conceived and outlined the manuscript, and edited the final manuscript; Xie YQ contributed to the writing and editing of the manuscript; Li CC and Yu MR performed the literature search; All authors were involved in discussion, and have read and approved the final manuscript.
Supported by the Zhejiang Provincial Natural Science Foundation of China, No. LTGC23H200005 and No. LQ19H160017; and the Medical Science and Technology Project of Zhejiang Province, China, No. 2022RC167.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jiang Cao, PhD, Professor, Center for Basic and Translational Research, the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou 310009, Zhejiang Province, China. caoj@zju.edu.cn
Received: May 27, 2024
Revised: July 29, 2024
Accepted: August 12, 2024
Published online: September 24, 2024
Processing time: 94 Days and 5.7 Hours
Abstract

Gastric signet-ring cell carcinoma (GSRCC) is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis. Studies have shown that early GSRCC has a good prognosis, while advanced GSRCC is insensitive to radiotherapy, chemotherapy or immune checkpoint blockade therapy. With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry, more detailed atlas of tumor microenvironment (TME) in GSRCC and its association with prognosis could be investigated extensively. Recently, two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME, manifested as highly immunosuppressive, leading to high immune escape. The TME of advanced GSRCC was enriched for immunosuppressive factors, including the loss of CXCL13+-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells. In addition, GSRCC was mainly infiltrated by follicular B cells. The increased proportion of SRCC was accompanied by a decrease in mucosa-associated lymphoid tissue-derived B cells and a significant increase in follicular B cells, which may be one of the reasons for the poor prognosis of GSRCC. By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism, more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

Keywords: Gastric signet-ring cell carcinoma; Single-cell RNA sequencing; Immunosuppressive tumor microenvironment; Immune checkpoint blockade therapy; Prognosis

Core Tip: Two single-cell RNA sequencing studies in 2023 revealed an immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma (GSRCC). Advanced GSRCC was enriched for immunosuppressive factors, including the loss of CXCL13+-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells. In addition, GSRCC was mainly infiltrated by follicular B cells. Distinct molecular characteristics and more effective immunotherapy strategies should be investigated to improve the clinical outcomes of GSRCC.