Immunogenicity of cancer cells: An overview

The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its proficiency in inciting an immunological response. The prowess of immunogenicity stands as a pivotal determinant in the triumph of formulating immunotherapeutic methodologies. Immunotherapeutic strategies include immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and on vaccines. Immunogenic cell death (ICD) epitomizes a form of cellular demise that incites an immune response against dying cells. ICD is characterized by the liberation of distinct specific molecules that activate the immune system, thereby leading to the identification and elimination of dying cells by immunocytes. One of the salient characteristics inherent to the ICD phenomenon resides in the vigorous liberation of adenosine triphosphate (ATP) by cellular entities dedicated to embarking upon the process of programmed cell death, yet refraining from complete apoptotic demise. ICD is initiated by a sequence of molecular events that occur during cell death. These occurrences encompass the unveiling or discharge of molecules such as calreticulin, high-mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) from dying cells. These molecules act as “eat me” signals, which are recognized by immune cells, thereby prompting the engulfment and deterioration of expiring cells by phagocytes including various pathways such as Necroptosis, Apoptosis, and pyroptosis. Here, we review our current understanding of the pathophysiological importance of the immune responses against dying cells and the mechanisms underlying their activation. Overall, the ICD represents an important mechanism by which the immune system recognizes and eliminates dying cells, including cancer cells. Understanding the molecular events that underlie ICD bears the potential to engender innovative cancer therapeutics that harness the power of the immune system to combat cancer.