Macrophage-Dendritic Cell-T-Cell Tetrads Orchestrate Antitumor Immunity and Response to Checkpoint Blockade.

ABSTRACT: Immune checkpoint inhibitors (ICIs) elicit durable responses in only a subset of patients with solid tumors, underscoring the need to define the cellular architectures that govern effective antitumor immunity. Here we identify a spatially organized multicellular immune unit comprising macrophages, cDC1s, CD4⁺ T-cells, and CD8⁺ T-cells that emerges in response to anti-CTLA-4 or dual checkpoint blockade. We term these structures tetrads. Using multiplexed imaging and spatial transcriptomics in mouse and human tumors, we show that tetrads assemble early during immune priming, depend on the ICOS-ICOSL pathway, and are enriched for ICOS⁺ Th1-like CD4⁺ T cells and ICOSL^high cDC1s. CD8⁺ T-cells within tetrads exhibit an acti

SUBMITTER: Chaib M 

PROVIDER: S-EPMC12776307 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature