Gefitinib enhances the anti ‑tumor immune response against EGFR‑mutated NSCLC by upregulating B7H5 expression and activating T cells via CD28H

Int J Oncol. 2022 Dec;61(6):146. doi: 10.3892/ijo.2022.5436. Epub 2022 Oct 7.ABSTRACTGefitinib is a sensitive and effective drug to treat non‑small‑cell lung cancer (NSCLC) carrying the somatic activating mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR). In the present study, a new mechanism of action of gefitinib in EGFR‑mutated NSCLC cells was discovered using in vitro co‑culture of NSCLC cells with peripheral blood mononuclear cells (PBMCs). Gefitinib significantly enhanced the cytotoxicity of PBMCs against NSCLC cells expressing mutated EGFR but not in cells expressing wild‑type EGFR. Furthermore, it was observed that B7H5 expression was significantly lower in EGFR‑mutant cells than in wild‑type cells, while inhibition of EGFR by gefitinib or reduction in EGFR using a small interfering RNA (siRNA) both increased the expression of B7H5 in EGFR‑mutated NSCLC cells. In addition, when B7H5 expression was reduced by siRNA, the toxic effect of gefitinib was reduced in the co‑culture of PBMCs and EGFR‑mutant NSCLC cells. In addition, the siRNA‑mediated decrease in expression of the B7H5 receptor CD28H in PBMCs also reduced the toxicity of gefitinib on EGFR‑mutated NSCLC. Based on these results, it may be proposed that the B7H5/CD28H axis is involved in NSCLC‑mediated immunosuppression when EGFR is overactivated. Gefitinib actively inhibits mutated EGFR, which induces B7H5 expression on the cell surface of NSCLC cells, t...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Source Type: research