| First Author | Ziblat A | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 5 | Pages | 114141 |
| PubMed ID | 38656869 | Mgi Jnum | J:350954 |
| Mgi Id | MGI:7658776 | Doi | 10.1016/j.celrep.2024.114141 |
| Citation | Ziblat A, et al. (2024) 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. Cell Rep 43(5):114141 |
| abstractText | 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 Batf3(+) DCs within the TME is associated with CD8(+) T cell transcriptional states linked to anti-PD-1 response. Our results demonstrate that Batf3(+) DCs within the TME are critical for PD-1/PD-L1 blockade efficacy and indicate a major role for the 4-1BB/4-1BB ligand (4-1BBL) axis during this process. |
