Pro-tumor Tfh2 cells induce detrimental IgG4 production and PGE₂-dependent IgE inhibition in pancreatic cancer.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and it is characterized by predominant pro-tumor Th2-type inflammation. T follicular helper (Tfh) cells are relevant immunoregulators in cancer, and often correlate with better survival. How the Th2-skewed microenvironment in PDAC modulates the differentiation of Tfh cells and their immunoregulatory function is unknown.

Methods

We carried out high-dimensional flow cytometry and T-cell receptor- and RNA-sequencing, as well as bioinformatics, immunohistochemistry and in vitro mechanistic studies.

Findings

We identified Tfh1-, Tfh2-, and Tfh17-like cell clusters in the blood, tumors and tumor-draining lymph-nodes (TDLNs) of chemo-naïve PDAC patients and showed that high percentages of Tfh2 cells wi

SUBMITTER: De Monte L 

PROVIDER: S-EPMC10542011 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature