Tissue-resident peripheral helper T cells foster hepatocellular carcinoma immune evasion by promoting regulatory B-cell expansion.
10.1097/CM9.0000000000003544
- Author:
Haoyuan YU
1
;
Mengchen SHI
2
;
Xuejiao LI
3
;
Zhixing LIANG
1
;
Kun LI
1
;
Yongwei HU
1
;
Siqi LI
1
;
Mingshen ZHANG
1
;
Yang YANG
1
;
Yang LI
1
;
Linsen YE
1
Author Information
1. Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
2. Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
3. Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, Guangdong 510630, China.
- Publication Type:Journal Article
- Keywords:
Hepatocellular carcinoma;
Immune escape;
Peripheral helper T cells;
Regulatory B cells
- MeSH:
Carcinoma, Hepatocellular/metabolism*;
Liver Neoplasms/metabolism*;
Humans;
T-Lymphocytes, Helper-Inducer/metabolism*;
Animals;
Mice;
Male;
Female;
Mice, Inbred C57BL;
Middle Aged;
B-Lymphocytes, Regulatory/metabolism*;
Flow Cytometry;
Interleukin-21;
Aged;
Chemokine CXCL13/metabolism*
- From:
Chinese Medical Journal
2025;138(17):2148-2158
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown.
METHODS:Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays.
RESULTS:T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression.
CONCLUSION:Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
