Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms

Pier Paolo Pandolfi and colleagues report that the genetic background of tumors in mice recruits specific immune-cell subsets, suggesting that precision medicine should account for both the tumor drivers and the distinct immune-cell microenvironments that they elicit. Multiple immune-cell types can infiltrate tumors and promote progression and metastasis through different mechanisms, including immunosuppression. How distinct genetic alterations in tumors affect the composition of the immune landscape is currently unclear. Here, we characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. We observed a striking quantitative and qualitative heterogeneity that was directly dependent on the specific genetic events in the tumor and ranged from 'cold', noninflamed tumors to massively infiltrated landscapes—results with important therapeutic implications. Further, we showed these qualitative differences in transcriptomic analysis of human prostate cancer samples. These data suggest that patient stratification on the basis of integrated genotypic–immunophenotypic analyses may be necessary for successful clinical trials and tailored precision immunological therapies.