Batf3⁺ DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy.

ABSTRACT: The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8⁺ T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3⁺ DCs and CD8⁺ T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to B

SUBMITTER: Ziblat A 

PROVIDER: S-EPMC11229087 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature