Cancer cells accelerate exhaustion of persistently activated mouse CD4⁺ T cells.

ABSTRACT: Most exhaustion studies have focused on CD8⁺ T cells. Here, we demonstrated reciprocal growth inhibition of CD4⁺ T cells and colorectal cancer cells, which induced the expression of PD-1, PD-L1, and PD-L2 in CD4⁺ T cells. The accelerated exhaustion of CD4⁺ T cells was evidenced by the reduced secretion of several cytokines, including IL-2, IFN-γ, or TNFα, and elevated secretion of CXCL family chemokines. Progressive expression of PD-L1, CTLA4, and IDO1 exhaustion markers occurred concomitantly with tumor growth in vivo in a mouse model. The pattern of CD4⁺ T cell exhaustion was analogous to that observed in CD8⁺ T cells, although with altered dynamics. The PD-L1-high phenotype can be induced by co-culture with tumor c

SUBMITTER: Stachowiak M 

PROVIDER: S-EPMC12184148 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature