PD-1/PD-L1 enhanced cisplatin resistance in gastric cancer through PI3K/AKT mediated P-gp expression

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

“…In addition, many long noncoding RNAs, circular RNAs, and micro RNAs were also involved in chemoresistance to cisplatin in hepatocellular carcinoma (Ding et al, 2019;Luo et al, 2019;Pratama et al, 2019). Notably, Cisplatin has been reported to increases PD-L1 expression in gastric cancer, nonsmall cell lung cancer (NSCLC), and hepatocellular carcinoma, while cisplatin in combination with PD-1/PD-L1 inhibitor can produce a synergic antitumor activity against hepatocellular carcinoma (Fournel et al, 2019;Li et al, 2020;Wu et al, 2021). Consistent with these reports, here we observed an increased expression of PD-L1 in cisplatin-treated HCC cells.…”

“…Clinical studies confirmed that the high expression of PD-L1 in HCC tissues is positively correlated with low overall survival of patients. Recently, accumulating evidences suggested that cisplatin could promote PD-L1 expression in lung cancer, gastric cancer, and bladder cancer; while blocking the PD-1/PD-L1 axis enhanced the antitumor effects of cisplatin in these malignant solid tumors (Fournel et al, 2019;Tsai et al, 2019;Wu et al, 2021). Although high expression of PD-L1 has also been observed in the microenvironment of hepatocellular carcinoma after cisplatin treatment (Li et al, 2020), however, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in HCC cells remains largely unknown.…”

Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells

“…However, unlike the treatment of ASA, treatment of NS-398, a selective inhibitor of COX-2, did not promote cell death and inhibit sphere formation significantly, suggesting that the effect of ASA was likely attributed to COX-2-independent pathways in ESCC. Interestingly, we found that ASA could reduce the efflux activity of ESCC cells by inhibiting PI3K signalling, which was reported to mediate P-glycoprotein (P-gp) expression and enhance DDP resistance [ 52 ]. This suggested that inhibition of PI3K signalling by ASA may contribute to overcoming DDP resistance.…”

Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng—A Promising Approach for Cancer Therapy

“…Generally, cancer cells could evade anti-tumor immunity by adopting active immunogenicity reduction strategies, including reduced expression of tumor antigens, diminished MHC-I expression for reduced antigenic recognition by T cells, and aberrant expression of immune checkpoint proteins, such as programmed death ligand-1 (PD-L1), which inhibits existing host anti-tumor immunity ( Kim and Seo, 2018 ; Looi et al, 2019 ; Tang et al, 2014 ). Furthermore, PD-L1 expression can be up-regulated in tumor cells that are resistant to chemotherapeutic agents ( Shen et al, 2019 ; Wu et al, 2021 ), including tumor-targeting drugs such as EGFR-TKI ( Peng et al, 2019 ), thus promoting immune escape of tumor cells. Although inhibitors targeting immune checkpoints have been developed and have become a focal point of clinical cancer therapy, current low treatment response rates, high incidence of side-effects, and acquired resistance are still unavoidable challenges.…”