PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma
Background A major current challenge is to exploit tertiary lymphoid structures (TLSs) to promote the lymphocyte infiltration, activation and differentiation by tumor antigens to increase antitumor immune responses. The mechanisms that underlie the role of TLS formation in the adaptive immune respon...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMJ Publishing Group
2021-07-01
|
Series: | Journal for ImmunoTherapy of Cancer |
Online Access: | https://jitc.bmj.com/content/9/7/e002101.full |
id |
doaj-9ea31ac4952542f9bea1a27c525694b2 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shu-Mei Yan Jiang-Ping Li Chang-You Wu Ming-Yuan Chen Shang-Xin Liu Yin-Feng Kang Cong Sun Jennifer R Grandis Mu-Sheng Zeng Qian Zhong |
spellingShingle |
Shu-Mei Yan Jiang-Ping Li Chang-You Wu Ming-Yuan Chen Shang-Xin Liu Yin-Feng Kang Cong Sun Jennifer R Grandis Mu-Sheng Zeng Qian Zhong PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma Journal for ImmunoTherapy of Cancer |
author_facet |
Shu-Mei Yan Jiang-Ping Li Chang-You Wu Ming-Yuan Chen Shang-Xin Liu Yin-Feng Kang Cong Sun Jennifer R Grandis Mu-Sheng Zeng Qian Zhong |
author_sort |
Shu-Mei Yan |
title |
PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma |
title_short |
PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma |
title_full |
PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma |
title_fullStr |
PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma |
title_full_unstemmed |
PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma |
title_sort |
pd-1+cxcr5−cd4+ th-cxcl13 cell subset drives b cells into tertiary lymphoid structures of nasopharyngeal carcinoma |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2021-07-01 |
description |
Background A major current challenge is to exploit tertiary lymphoid structures (TLSs) to promote the lymphocyte infiltration, activation and differentiation by tumor antigens to increase antitumor immune responses. The mechanisms that underlie the role of TLS formation in the adaptive immune responses against nasopharyngeal carcinoma (NPC) remain largely unknown.Methods Cell populations and the corresponding markers were identified by single-cell RNA sequencing and fluorescence-activated cell sorting analysis. In vitro differentiation experiments were used to simulate the generation, regulation and function of the Th-CXCL13 cell subset in the tumor microenvironment of NPC. These were followed by histological evaluation of the colocalization of tumor-associated B cells (TABs) and Th-CXCL13 cells within TLSs, and statistical analysis of the relationship between the cells in TLSs and overall survival.Results A PD-1+CXCR5−CD4+ Th-CXCL13 cell subset was identified in NPC. This subset was a major source of CXCL13, representing the majority of the CD4+ T cells at levels comparable with Th1 and Tfh cells present in the TLSs. Monocytes activated by toll-like receptor 4 agonists served as the antigen-presenting cells that most efficiently triggered the expansion of Th-CXCL13 cells. Transforming growth factor beta 1 (TGF-β1) stimulation and activation of Sox4 were critical for the induction and polarization of Th-CXCL13 cells in this process. The potential functional contributions of TABs recruited by Th-CXCL13 cells which induced plasma cell differentiation and immunoglobulin production via interleukin-21 and CD84 interactions in the TLSs demonstrated improved survival.Conclusions Induction of Th-CXCL13 cells links innate inflammation to immune privilege in tumor-associated TLSs and might predict better survival. |
url |
https://jitc.bmj.com/content/9/7/e002101.full |
work_keys_str_mv |
AT shumeiyan pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT jiangpingli pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT changyouwu pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT mingyuanchen pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT shangxinliu pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT yinfengkang pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT congsun pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT jenniferrgrandis pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT mushengzeng pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma AT qianzhong pd1cxcr5cd4thcxcl13cellsubsetdrivesbcellsintotertiarylymphoidstructuresofnasopharyngealcarcinoma |
_version_ |
1721222206162206720 |
spelling |
doaj-9ea31ac4952542f9bea1a27c525694b22021-08-04T16:30:29ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-07-019710.1136/jitc-2020-002101PD-1+CXCR5−CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinomaShu-Mei Yan0Jiang-Ping Li1Chang-You Wu2Ming-Yuan Chen3Shang-Xin Liu4Yin-Feng Kang5Cong Sun6Jennifer R Grandis7Mu-Sheng Zeng8Qian Zhong9Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaInstitute of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of ChinaSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaDepartment of Otolaryngology–Head and Neck Surgery, University of California, San Francisco, California, USASun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of ChinaBackground A major current challenge is to exploit tertiary lymphoid structures (TLSs) to promote the lymphocyte infiltration, activation and differentiation by tumor antigens to increase antitumor immune responses. The mechanisms that underlie the role of TLS formation in the adaptive immune responses against nasopharyngeal carcinoma (NPC) remain largely unknown.Methods Cell populations and the corresponding markers were identified by single-cell RNA sequencing and fluorescence-activated cell sorting analysis. In vitro differentiation experiments were used to simulate the generation, regulation and function of the Th-CXCL13 cell subset in the tumor microenvironment of NPC. These were followed by histological evaluation of the colocalization of tumor-associated B cells (TABs) and Th-CXCL13 cells within TLSs, and statistical analysis of the relationship between the cells in TLSs and overall survival.Results A PD-1+CXCR5−CD4+ Th-CXCL13 cell subset was identified in NPC. This subset was a major source of CXCL13, representing the majority of the CD4+ T cells at levels comparable with Th1 and Tfh cells present in the TLSs. Monocytes activated by toll-like receptor 4 agonists served as the antigen-presenting cells that most efficiently triggered the expansion of Th-CXCL13 cells. Transforming growth factor beta 1 (TGF-β1) stimulation and activation of Sox4 were critical for the induction and polarization of Th-CXCL13 cells in this process. The potential functional contributions of TABs recruited by Th-CXCL13 cells which induced plasma cell differentiation and immunoglobulin production via interleukin-21 and CD84 interactions in the TLSs demonstrated improved survival.Conclusions Induction of Th-CXCL13 cells links innate inflammation to immune privilege in tumor-associated TLSs and might predict better survival.https://jitc.bmj.com/content/9/7/e002101.full |