Abstract IA09: Non-cell autonomous regulation of senescence in cancer and cancer therapy

Abstract

Abstract Loss of the tumor suppressor gene PTEN opposes malignant transformation by triggering a cellular senescence response. This process is finely tuned by both cell-autonomous and non-cell-autonomous mechanisms that regulate the entry of tumor cells to senescence. I will discuss recent findings demonstrating that at the onset of senescence, PTEN null prostate tumors are infiltrated by a population of CD11b+Gr-1+ myeloid cells that protect a fraction of proliferating tumor cells from senescence, thus sustaining tumor growth. Mechanistically, I found that Gr-1+ cells antagonize senescence in a paracrine manner by interfering with the senescence-associated secretory phenotype (SASP) of the tumor through the secretion of interleukin-1 receptor antagonist. Therapeutically, I will present evidence that therapy-induced senescence and efficacy can be enhanced in PTEN null tumors by treatment that affect the recruitment of tumor-infiltrating CD11b+Gr-1+ myeloid cells or that reprogram the SASP. Taken together these data identify a novel non-cell-autonomous network, established by the innate immunity, that controls senescence evasion and chemoresistance in cancer. Targeting this network provides novel opportunities for cancer therapy. Citation Format: Andrea Alimonti. Non-cell autonomous regulation of senescence in cancer and cancer therapy. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA09.