Great ideas and discussion about necrosis triggers and consequences with my co-speakers Jose Androver at the Francis Crick and Carlos Carmona-Fontaine at NYU!
SY42 – The Necrotic Tumor Microenvironment as an Instigator of Metastatic Aggression and Immuno-evasion
Necrotic cell death is a feature of many aggressive fast-growing tumors. Necrosis is typically thought of as simply a correlative feature, but emerging studies now reveal an active role for necrosis in driving drug-resistant and metastatic plasticity states. Recent studies, described by Jose M. Adrover, indicate that cancer-elicited neutrophil populations can induce thrombo-inflammatory occlusion of tumor vessels, leading to downstream ischemia and necrosis, in turn, driving tumor evolution toward a more aggressive, metastatic phenotype. These neutrophils represent a remotely cancer-driven onco-fetal reversion of hematopoiesis, and they can be targeted to enhance therapeutic responses. From a complementary perspective, necrotic cores harbor ischemic and metabolic stresses but also create sublethal conditions that allow tumor cells to avoid immune detection. Development of experimental systems, described by Carlos Carmona-Fontaine, enable modeling the formation of necrotic cores, which are used to screen for perturbations that restore the immune response to tumors. Finally, recent studies on metastatic tumor dissemination, described by Kevin Cheung, reveal how the necrotic core is a driver of tumor adaptations that promote circulating tumor cell and circulating tumor cell cluster spread. Epidemiologic studies in human breast cancer cohorts, along with genetic and pharmacologic blockade of tumor-elicited signals, highlight tumor necrosis as a preventable process and determinant of future metastatic potential. In total, this session highlights the emerging biology of the necrotic tumor microenvironment as a therapeutic target, across complementary perspectives, experimental methods, and cancer systems.
