Tumor cell heterogeneity drives spatial organization of the intratumoral immune response in squamous cell skin carcinoma.

ABSTRACT: Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy and an inferior anti-tumor immune response. The underlying mechanism of this association is unknown. To address this question, we modeled heterogeneous tumors comprised of a pro-inflammatory ("hot") and an immunosuppressive ("cold") tumor population, labeled with YFP and RFP tags respectively to enable precise spatial tracking. The resulting mixed-population tumors exhibited distinct regions comprised of YFP⁺ (hot) cells, RFP⁺ (cold) cells, or a mixture. We found that tumor regions occupied by hot tumor cells (YFP⁺) harbored more total T cells and a higher frequency of Th1 cells and IFNγ⁺ CD8 T cells compared to regions

SUBMITTER: Tanaka M 

PROVIDER: S-EPMC10168251 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature