Apoptosis: aJanus bifronsin T-cell immunotherapy

Abstract

Immunotherapy has revolutionized the treatment of cancer. In particular, immune checkpoint blockade, bispecific antibodies, and adoptive T-cell transfer have yielded unprecedented clinical results in hematological malignancies and solid cancers. While T cell-based immunotherapies have multiple mechanisms of action, their ultimate goal is achieving apoptosis of cancer cells. Unsurprisingly, apoptosis evasion is a key feature of cancer biology. Therefore, enhancing cancer cells’ sensitivity to apoptosis represents a key strategy to improve clinical outcomes in cancer immunotherapy. Indeed, cancer cells are characterized by several intrinsic mechanisms to resist apoptosis, in addition to features to promote apoptosis in T cells and evade therapy. However, apoptosis is double-faced: when it occurs in T cells, it represents a critical mechanism of failure for immunotherapies. This review will summarize the recent efforts to enhance T cell-based immunotherapies by increasing apoptosis susceptibility in cancer cells and discuss the role of apoptosis in modulating the survival of cytotoxic T lymphocytes in the tumor microenvironment and potential strategies to overcome this issue.

The role of programmed cell death in diabetic foot ulcers

“…Apoptosis, which is a form of programmed cell death, is an active process regulated by specific genes. Apoptosis is a normal physiological response of cells that culminates in the engulfment of apoptotic cells by phagocytes 9 . Apoptosis can generally be divided into three stages.…”

“…Apoptosis is a normal physiological response of cells that culminates in the engulfment of apoptotic cells by phagocytes. 9 Apoptosis can generally be divided into three stages. The first stage includes the disappearance of cell–cell contacts, while the plasma membrane remains intact.…”

Targeted Therapy for EWS-FLI1 in Ewing Sarcoma

“…Metabolic or epigenetic reprogramming to enhance the function of T-cells provides another therapeutic option [ 214 ]. Apart from leading apoptosis, the PARP inhibitor modulates the tumor microenvironment by activating the cGAS-STING pathway and, thus, enables low-dose CAR-T-cells with higher efficacy [ 215 , 216 ]. Olaparib also suppresses myeloid-derived suppressor cell migration via the SDF1α/CXCR4 axis and promotes the survival of CD8+ T-cells in tumor tissue [ 217 ].…”

“…Through multiple pathways, the purpose of T-cell therapy is to achieve the apoptosis of cancer cells [ 216 ]. LSD1 inhibition promotes tumor immunogenicity and T-cell infiltration [ 218 ].…”

Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy

“…Immunotherapy represents a promising therapeutic approach with minimal toxicity and sustained efficacy, achieved through the augmentation of the body’s immune response for precise targeting of cancer cells. − Furthermore, it can facilitate the formation of immune memory, empowering the immune system to efficiently combat potential cancer recurrence. The successful eradication of cancer cells via the immune system hinges not only on the induction of cancer-specific T cells but also on efficacious physical interactions between T cells and cancer cells .…”