The Progression of Cell Death Affects the Rejection of Allogeneic Tumors in Immune-Competent Mice – Implications for Cancer Therapy

摘要: Large amounts of dead and dying cells are produced during cancer therapy allograft rejection. Depending on the death pathway stimuli involved, exhibit diverse features resulting in defined physiological consequences for host. It is not fully understood how modulate immune response To address this problem, different were studied B16F10 melanoma by inducible transgene expression pro-apoptotic active forms caspase-3 (revCasp-3), Bid (tBid), Mycobacterium tuberculosis-necrosis inducing toxin (CpnTCTD). The outcome elicited each stimulus was assessed evaluating rejection tumors implanted subcutaneously BALB/c mice immunized with cells. Expression all proteins efficiently killed vitro (>90%) displayed distinctive morphological as multiparametric flow cytometry analysis. allogeneic expressing revCasp-3 or CpnTCTD showed strong challenge. In contrast, either after tBid irradiation UVB did not, suggesting an immunologically silent cell death. Surprisingly, immunogenic induced correlated elevated intracellular ROS levels at time-point immunization. Conversely, early mitochondrial dysfunction accounted absence accumulation time point Although inhibition sufficient to abrogate immunogenicity our allo-immunization model, we suggest that generation may be important factor its role DAMP development responses.