An intriguing aspect of the tumor suppressor p53 is its ability to communicate to the adaptive immune system and control the cytotoxic T-lymphocyte (CTL) response to cancer cells. Wild-type p53 (wtp53) communicates with CTLs through proteins involved in the major histocompatibility complex (MHC) class I antigen presentation pathway [e.g., transporter associated with antigen processing 1 (TAP1) and endoplasmic reticulum amino peptidase 1 (ERAP1)], the apoptosis signal receptor Fas/APO-1, and the inhibitory immune-checkpoint programmed death-ligand 1 (PD-L1). The presence of wtp53 in cancer cells ultimately promotes effector CTL-induced tumor cell death. Analogously, wtp53 in tumors unleashes the CTL response via inhibition of PD-L1 and enhances their effectiveness by upregulating Fas/APO-1 and MHC I. Given that p53 is mutated in approximately 50% of human cancers and also impacts the immunoreactivity of cancer cells, a significant number of patients can be affected by the impaired CTL response that results from non-functional p53. An attenuated CTL response due to p53 mutations could decrease response rates to immunotherapeutic drugs, leading to poor patient prognoses. This review article will summarize how p53 can regulate the cell-mediated adaptive immune response to cancer.
Conflicts of Interest: The authors have no conflicts of interest to declare.
