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Supplementary Methods from Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization

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posted on 2023-04-03, 21:00 authored by Min-Min Chen, Xiao Xiao, Xiang-Ming Lao, Yuan Wei, Rui-Xian Liu, Qiu-Hui Zeng, Jun-Cheng Wang, Fang-Zhu Ouyang, Dong-Ping Chen, Ka-Wo Chan, Dai-Chao Shi, Limin Zheng, Dong-Ming Kuang

Supplementary Methods. Isolation of Mononuclear Cells from Peripheral Blood and Tissues; Flow Cytometry (FACS); ELISA; Real-Time PCR; Construction of Viral Vectors; Ex Vivo Plasma Cell Induction; Statistical Analysis.

Funding

National Natural Science Foundation of China

the National Key Research and Development Plan of China

Guangdong Natural Science

Foundation for the Author of National Excellent Doctoral Dissertation of PR China

Fundamental Research Funds for the Central Universities

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ARTICLE ABSTRACT

The existence, regulation, and functions of IL21+ immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21+ TFH-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4+ T-cell population at levels comparable with the TFH cells present in lymph nodes. However, these TFH-like cells displayed a unique CXCR5−PD-1lo/−BTLA−CD69hi tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of TFH cells. Toll-like receptor 4 (TLR4)–elicited innate monocyte inflammation was important for IL21+ TFH-like cell induction in tumors, and activation of STAT1 and STAT3 was critical for TFH-like cell polarization in this process. Importantly, the TFH-like cells operated in IL21–IFNγ-dependent pathways to induce plasma cell differentiation and thereby create conditions for protumorigenic M2b macrophage polarization and cancer progression. Thus, induction of TFH-like cells links innate inflammation to immune privilege in tumors.Significance: We identified a novel protumorigenic IL21+ TFH-like cell subset with a CXCR5−PD-1− BTLA−CD69hi tissue-resident phenotype in hepatoma. TLR4-mediated monocyte inflammation and subsequent T-cell STAT1 and STAT3 activation are critical for TFH-like cell induction. TFH-like cells operate via IL21–IFNγ pathways to induce plasma cells and create conditions for M2b macrophage polarization. Cancer Discov; 6(10); 1182–95. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069

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