Immunogenic cell death (ICD) in cancer: From plasticity and discovery of immunogenic determinants to anticancer vaccination.

Most anti-cancer modalities kill cancer cells via physiological apoptosis (a cell death routine that actively suppresses immunity). Recently, certain anticancer drugs were shown to induce an apoptotic routine called immunogenic cell death (ICD) that is immunostimulatory due to the associated emission of immunogenic determinants like calreticulin (CRT) and ATP, which help to stimulate anti-tumor immunity that “vaccinates” the host against the tumor. We have reported that one of such therapies (photodynamic therapy or PDT) causes induction of bona fide ICD that is technically and mechanistically more robust than chemotherapy-induced ICD. However, it has been observed that blocking emission of these determinants only partially reduces the vaccination potential of cancer cells undergoing ICD. This raises the possibility of as-yet-unknown ICD determinants. Besides this, it is also crucial to translate ICD, pre-clinically, for clinical cancer immunotherapy. To this end, the major aims of this project are; (1) to fully understand the role of CRT/ATP in ICD, (2) to identify new ICD determinants and (3) to capitalize on this knowledge and translate the concept of PDT-induced ICD preclinically for the betterment of dendritic cell-based vaccination strategies against glioblastoma. While elucidating the role of known determinants and identifying new determinants would pave way for revising the concept of ICD; yet its preclinical translation would pave way for future clinical application of ICD in cancer patients.