Cytotoxic CD4⁺ T cells exhibit an immunosuppressive shift in checkpoint immunotherapy resistance in melanoma patients.

ABSTRACT: Although checkpoint immunotherapy has primarily focused on CD8⁺ T cells, emerging evidence highlights an important role for cytotoxic CD4⁺ T cells in mediating therapeutic responses. However, research on the functional properties of cytotoxic CD4⁺ T cells in the context of immunotherapy is still at an early stage and remains insufficiently defined. Utilizing single-cell RNA-sequencing datasets obtained from metastatic melanoma patients treated with checkpoint inhibitors targeting PD-1 and/or CTLA-4, we performed transcriptomic profiling of conventional CD4⁺ T cells, excluding proliferative and regulatory (FOXP3⁺) subsets, and compared responders and non-responders as distinct groups. Importantly, our analysis identified distinct clusters that discriminate between responders and non-respond

SUBMITTER: Bae HR 

PROVIDER: S-EPMC12411337 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature