ITGB1 is a TNBC tumor microenvironment-dependent immune modulator

Tumorigenesis and metastasis, as well as insufficient response and the emergence of resistance to immunotherapy, are frequently attributed to the intricate interplay between cancer cells and tumor microenvironment (TME). Cancer cells significantly contribute to the recruitment of tumor-infiltrating leukocytes, which, in turn, directly regulate cancer cell proliferation and viability. Comprehending the mechanism and key regulators of the crosstalk between cancer cells and immune components in the TME is imperative for developing efficacious immunotherapeutic interventions. Here, through an in vivo CRISPR screen targeting cell surface genes, we identify ITGB1 as a central arbiter dictating the tumorigenicity of triple-negative breast cancer (TNBC). ITGB1 mediates the establishment of pro-tumorigenic TME by orchestrating tumor-associated myeloid populations and impeding T cell infiltration, while transducing pro-survival signaling from the tumor-favorable milieu into TNBC cells, to bolster tumor development.