Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer

Distinct T cell infiltration patterns, i.e., immune infiltrated, excluded, and desert, result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these tumor immune phenotypes remain elusive. Here, we provide a high-resolution dissection of the entire tumor ecosystem through single-cell RNA-sequencing analysis of 15 ovarian tumors. Immune-desert tumors are characterized by unique tumor cell-intrinsic features, including metabolic pathways and low antigen presentation, and an enrichment of monocytes and immature macrophages. Immune-infiltrated and -excluded tumors differ markedly in their T cell composition and fibroblast subsets. Furthermore, our study reveals chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumor cell-T cell cross talk via CXCL16-CXCR6 and stromal-immune cell cross talk via CXCL12/14-CXCR4. Our data highlight potential molecular mechanisms that shape the tumor immune phenotypes and may inform therapeutic strategies to improve clinical benefit from cancer immunotherapies. [Display omitted] •OXPHOS and IFN gene sets are enriched in infiltrated and excluded tumor cells.•Pre-dysfunctional CD8+ GZMK T cells are enriched in excluded tumors.•FCN1 monocytes and immature MARCO macrophages are enriched in desert tumors.•CXCL16 is expressed primarily by infiltrated tumor cells and CXCR6 by T cells. Hornburg et al. dissected the composition of the ovarian tumor microenvironment by scRNA-seq to define the underlying biology of the T cell infiltration pattern, namely the tumor immune phenotypes. The identified features, including the enrichment of immature myeloid cells in desert tumors, may help inform immunotherapeutic strategies in ovarian cancer.