p53 mutation and deletion contribute to tumor immune evasion

Abstract

TP53 (or p53) is widely accepted to be a tumor suppressor. Upon various cellular stresses, p53 mediates cell cycle arrest and apoptosis to maintain genomic stability. p53 is also discovered to suppress tumor growth through regulating metabolism and ferroptosis. However, p53 is always lost or mutated in human and the loss or mutation of p53 is related to a high risk of tumors. Although the link between p53 and cancer has been well established, how the different p53 status of tumor cells help themselves evade immune response remains largely elusive. Understanding the molecular mechanisms of different status of p53 and tumor immune evasion can help optimize the currently used therapies. In this context, we discussed the how the antigen presentation and tumor antigen expression mode altered and described how the tumor cells shape a suppressive tumor immune microenvironment to facilitate its proliferation and metastasis.

Successful treatment of pulmonary lymphomatoid granulomatosis with PD-1 inhibitor-based regimen: A Case Report and Literature Review

“…Upregulated p53 mediates cell cycle arrest and apoptosis, eliminating damaged cells [15] when oncogenic signals are present. In contrast, mutated p53 may increase PD-L1 expression by activating various cytokines, leading to the conversion of in ltrating T into depleted CD8 + T cells, counteracting the effects of PD-1 inhibitors [14]. However, our patient showed high P53 expression in immunohistochemistry, while intriguingly, NGS analysis did not reveal any mutation in the P53 gene.…”

“…As for tumor immune escape, Berger [13] concluded that PD-1, an immune checkpoint belonging to the immunoglobulin B7-CD28 family, plays a negative regulatory role in the human immune response by inhibiting T cell activation, proliferation, and inducing T cell death [13]. Suppression of PD-1 results in a signi cant reduction in T cells numbers, leading to immune evasion by tumor cells [14]. Therefore, PD-1 blockade can attenuate the inhibitory effect on T cell activation, fostering the activation of the endogenous anti-tumor immune response and providing a novel therapeutic pathway for tumor patients.…”

Integrated multi-omics profiling reveals a clinically relevant molecular feature and potential therapeutic target on phyllodes tumors of breast

“…In our results, both FAs and PTs harbor a variety of mutations, including missense, nonsense, frame-shift, insertion, and deletion, while the most frequent ones are missense mutations. These mutations likely involve a crucial region, such as a catalytic site or an interaction domain, to cause the loss of its original functions, including regulation of transcription [ 19 , 20 ], aberrant activation, or loss of signaling pathways [ 21 ]. We constructed the interaction network between the specific mutation and expression profiles to find the core mutated genes and their probable regulation on target genes.…”

Molecular mechanisms and therapeutic applications of huaier in breast cancer treatment

“…Other studies have also shown a significant increase in the percentage of positive TUNEL staining in breast cancer cells treated with Huaier (Wang et al, 2012;Qi et al, 2016). Activation of p53 leads to apoptosis (Liu et al, 2023). Zhang et al showed that p53 accumulated and was activated in MCF-7 cells in response to Huaier treatment (Zhang et al, 2010).…”