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.
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We thank the members of the laboratory of P.P.P. for critically reading and discussing the manuscript. We thank N. Pandell of the Preclinical Murine Pharmacogenetics Core at BIDMC, K. Berry and the members of the Center of Life Science animal facility for helping with all in vivo work. We thank the members of the Dana Farber Flow Cytometry Facility and the BIDMC Flow Cytometry Core for the help with all cell sorting. We also thank the Small Animal Imaging Core at BIDMC for the magnetic resonance imaging (MRI) work. This work was funded by NIH grants R01 CA102142 and R35 CA197529 awarded to P.P.P. and was supported by a Jane Coffin Childs Postdoctoral Fellowship to M.B.
The authors declare no competing financial interests.
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Bezzi, M., Seitzer, N., Ishikawa, T. et al. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms. Nat Med 24, 165–175 (2018). https://doi.org/10.1038/nm.4463
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