PD-1 Suppresses Human CD38 Circulating Tfr Cells and Regulates Humoral Immunity

Overview

Journal J Immunother Cancer

Date 2025 Jan 12

PMID 39800377

Authors

Heng Zhang

Hui Zheng

Yanchun Wang

Cuncun Chen

Ying Tong

Suhong Xie

Xiaolu Ma

Lin Guo

Renquan Lu

Affiliations

Soon will be listed here.

Abstract

Background: Anti-programmed cell death protein 1 (anti-PD-1) antibodies have achieved revolutionary success in cancer therapy. However, the impact of anti-PD-1 therapy on host humoral immunity in humans during cancer immunotherapy requires further investigation.

Methods: We evaluated immunoglobulin titers by ELISA and screened the immune landscape of immune cells from 25 healthy donors and 50 cases including 25 new-onset hepatocellular carcinoma (HCC) patients prior to systemic treatment and 25 HCC patients undergoing anti-PD-1 therapy by multicolor flow cytometry. Flow or beads sorted cells were cultured ex vivo for proliferation and functional analysis.

Results: Anti-PD-1 therapy significantly increased the levels of IgG and IgA in the periphery of HCC patients. Anti-PD-1 treatment led to an increase in plasmablasts and a notable rise in circulating T follicular regulatory (cTfr) cells, while changes in circulating B cells, T follicular helper cells, or regulatory T cells were not significant. Anti-PD-1 therapy also influenced the proliferation and function of cTfr cells, promoting the differentiation of CD38 cTfr cells. We observed that the CD38 Tfr cell subset in the peripheral blood can promote plasmablast differentiation, associated with altered antibody production.

Conclusions: Together, these data demonstrate the immunomodulatory role of PD-1 in restricting the differentiation and function of human cTfr cells and in regulating humoral immunity.

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