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- W2562783999 abstract "Cellular senescence is a stable growth arrest that constrains cell cycle progression in case proliferation becomes aberrant, thus limiting tumorigenesis. Oncogenic mutations and loss of tumor suppressor genes that cause uncontrolled cell-cycle progression are required events in tumor development. Nevertheless, many of these genetic alterations retain an intrinsic tumor-suppressive potential that gives rise to oncogene-induced senescence and tumor suppressor loss-induced senescence. Interestingly, many evidences support the idea that a strong interplay occurs between senescence, cancer cells, and tumor infiltrating immune populations, thus opening at the possibility to tune such interplay for cancer treatment. Indeed, tumor infiltrating T helper 1 cells can drive senescence in cancers in a cytokine-induced manner, by secreting IFNγ and TNFα in the tumor microenvironment. In addition, we recently described a model where Pten loss induced senescence is hindered in prostate tumor by non-cell-autonomous mechanisms. Our study support a model where tumor-infiltrating CD11b+Gr-1+ myeloid cells paracrinally triggers tumor senescence evasion in the prostate of Pten null mice, eventually promoting tumor progression. These findings we’ll be discussed. Interestingly, we will present new evidences from our lab indicating that M1 macrophages are polarized to the M2 phenotype in both Pten pc-/- and that treatments that interfere with the M1-M2 polarization and switch the skewing to the M1 polarization profile can induce senescence in Pten; Trp53pc-/- invasive prostate cancer tumours thereby arresting tumour progression. These findings open at the possibility that M1 directly control senescence in tumor cells. Finally, we have identified a gene expression signature that distinguishes myeloid infiltration in tumors and can be used as a predictive marker for tumor progression in prostate cancer patients. These evidences we’ll be also discussed. Citation Format: Diletta Di Mitri, JingJing Chen, Andrea Alimonti. Targeting the tumor immune response for pro-senescence therapy in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2346. doi:10.1158/1538-7445.AM2015-2346" @default.
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- W2562783999 date "2015-08-01" @default.
- W2562783999 modified "2023-09-27" @default.
- W2562783999 title "Abstract 2346: Targeting the tumor immune response for pro-senescence therapy in prostate cancer" @default.
- W2562783999 doi "https://doi.org/10.1158/1538-7445.am2015-2346" @default.
- W2562783999 hasPublicationYear "2015" @default.
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