Follicular Helper T Cells Remodel the Immune Microenvironment of Pancreatic Cancer via Secreting CXCL13 and IL-21

Xuan Lin; Longyun Ye; Xu Wang; Zhenyu Liao; Jia Dong; Ying Yang; Rulin Zhang; Hao Li; Pengcheng Li; Lei Ding; Tianjiao Li; Wuhu Zhang; Shuaishuai Xu; Xuan Han; Huaxiang Xu; Wenquan Wang; Heli Gao; Xianjun Yu; Liang Liu

doi:10.3390/cancers13153678

Cancers (Jul 2021)

Follicular Helper T Cells Remodel the Immune Microenvironment of Pancreatic Cancer via Secreting CXCL13 and IL-21

Xuan Lin,
Longyun Ye,
Xu Wang,
Zhenyu Liao,
Jia Dong,
Ying Yang,
Rulin Zhang,
Hao Li,
Pengcheng Li,
Lei Ding,
Tianjiao Li,
Wuhu Zhang,
Shuaishuai Xu,
Xuan Han,
Huaxiang Xu,
Wenquan Wang,
Heli Gao,
Xianjun Yu,
Liang Liu

Affiliations

Xuan Lin: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Longyun Ye: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Xu Wang: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Zhenyu Liao: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Jia Dong: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Ying Yang: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Rulin Zhang: Department of Laboratory Medicine, Shanghai General Hospital, Shanghai 200080, China
Hao Li: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Pengcheng Li: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Lei Ding: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Tianjiao Li: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Wuhu Zhang: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Shuaishuai Xu: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Xuan Han: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Huaxiang Xu: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Wenquan Wang: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Heli Gao: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Xianjun Yu: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Liang Liu: Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China

DOI: https://doi.org/10.3390/cancers13153678
Journal volume & issue: Vol. 13, no. 15
p. 3678

Abstract

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Immunosuppression is an important factor for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Follicular helper T cells (Tfh cells) play an anti-tumor role in various malignant solid tumors and predict better patient prognosis. In the present study, we aimed to determine the immunosuppressive mechanism associated with Tfh cells and explore a new strategy to improve the tumor microenvironment of PDAC. Flow cytometry was used to detect the infiltration and proportion of Tfh cells in tumor tissues and peripheral blood from patients with PDAC. The spatial correlations of Tfh cells with related immune cells were evaluated using immunofluorescence. The function of Tfh cells was examined using in vitro and in vivo model systems. The high infiltration of Tfh cells predicted better prognosis in patients with PDAC. Tfh cells recruited CD8+ T cells and B cells by secreting C-X-C motif chemokine ligand 13 (CXCL13), and promoted the maturation of B cells into antibody-producing plasma cells by secreting interleukin 21 (IL-21), thereby promoting the formation of an immunoactive tumor microenvironment. The function of Tfh cells was inhibited by the programmed cell death 1 ligand 1 (PD-L1)/programmed cell death 1 (PD-1) signaling pathway in PDAC, which could be reversed using neoadjuvant chemotherapy. Treatment with recombinant CXCL13, IL-21 and Tfh cells alleviated tumor growth and enhanced the infiltration of CD8+ T cells and B cells, as well as B cell maturation in a PDAC mouse model. Our results revealed the important role of Tfh cells in mediating anti-tumor cellular immunity and humoral immunity in PDAC via secreting CXCL13 and IL-21 and determined a novel mechanism of immunosuppression in PDAC.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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