♦️Cancer cells use complex mechanisms to evade immune surveillance, with inhibition of apoptotic signaling being a key strategy. Apoptosis, or programmed cell death, is an important process of self-destruction of damaged or dysfunctional cells that prevents malignancy and maintains tissue homeostasis. In cancer, this pathway is often disrupted, allowing tumor cells to survive and proliferate uncontrollably.
♦️Key anti-apoptotic proteins such as BCL-2, BCL-XL, and MCL-1 are frequently overexpressed in cancer cells, inhibiting the intrinsic apoptotic pathway by sequestering pro-apoptotic factors such as BAX and BAK. Similarly, mutations in TP53, a key tumor suppressor gene that regulates apoptosis, further reduce the immune system’s ability to eliminate malignant cells. Extrinsic apoptosis, triggered by death receptors such as Fas or TRAIL-R, can also be impaired, as cancer cells downregulate these receptors or upregulate decoy receptors to evade immune-mediated killing.
♦️In addition to the intrinsic and extrinsic pathways, the tumor microenvironment (TME) also plays an important role in protecting cancer cells from apoptosis. Factors secreted by tumor-associated stromal and immune cells, such as interleukin 10 (IL-10) and transforming growth factor-ẞ (TGF-β), create an immunosuppressive environment. These factors inhibit cytotoxic T cells and natural killer (NK) cells, thereby reducing their ability to induce apoptosis in cancer cells.
In summary, understanding the inhibition of apoptotic signaling in immune evasion is critical to advancing cancer immunotherapy. Strategies such as targeting anti-apoptotic proteins, reactivating death receptors, or reprogramming the TME are promising. If these approaches are combined with existing therapies such as immune checkpoint inhibitors and CAR-T cells, they can significantly enhance anti-tumor immunity and improve patient outcomes.
JYOTI