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06-12-2022 | Breast Cancer | Research

CXCL9 influences the tumor immune microenvironment by stimulating JAK/STAT pathway in triple-negative breast cancer

Authors: Lei Wu, Shengnan Sun, Fei Qu, Meili Sun, Xiuxiu Liu, Quanye Sun, Lin Cheng, Yan Zheng, Guohai Su

Published in: Cancer Immunology, Immunotherapy | Issue 6/2023

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and limited effective treatment options. Notably, immunotherapy is a potential therapeutic approach for TNBC. This study performed single-cell RNA sequencing on TNBC and found highly expressed CXCL9 in M1 macrophages. An intercellular communication network was found between M1 macrophages and M2 macrophages, and M1 macrophages could differentiate into M2 macrophages over time. Meanwhile, CXCL9 expression started to decrease in association with cell differentiation from M1 macrophages to M2 macrophages. Additionally, the M1 macrophage had strong connections to the M2 macrophage in the MHC-II signaling network. Through GSVA analysis, the MHC-II pathway activity of the M1 macrophages was significantly stronger than that of the M2 macrophages. Furthermore, CXCL9 was enriched in the MHC-II signaling pathway. CXCL9 was significantly enriched in the JAK/STAT signaling pathway. Western blot revealed that CXCL9 overexpression promotes JAK1/STAT2 expression in MDA-MB-231 cells. These findings indicate that CXCL9 is a potential clinical biomarker of prognosis and immunotherapy efficacy for TNBC patients. Also, it stimulates JAK/STAT activity, which in turn modifies the tumor microenvironment.

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Title: CXCL9 influences the tumor immune microenvironment by stimulating JAK/STAT pathway in triple-negative breast cancer
Authors: Lei Wu
Shengnan Sun
Fei Qu
Meili Sun
Xiuxiu Liu
Quanye Sun
Lin Cheng
Yan Zheng
Guohai Su
Publication date: 06-12-2022
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 6/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-022-03343-w

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