high expressing PD-L1 linked to reduced survival in NSCLC -
By Laura Cowen, medwireNews Reporter
Overexpression of programmed death ligand-1 (PD-L1) is independently associated with the presence of the receptor for epidermal growth factor ( EGFR ) genetic mutations and poor prognosis in patients with non-small cell lung cancer (NSCLC), of Japanese researchers report.
Isamu Okamoto (Kyushu University Hospital, Fukuoka) and colleagues explain that the binding of PD-L1 with its corresponding PD1 protein induces apoptosis in activated T cells, but blocking this interaction can improve the antitumor activity of T lymphocytes
Indeed, recent clinical trials have shown that blocking of the PD1-PD-L1 interaction with specific antibodies provides a clinical response in a subset of individuals with advanced NSCLC.
To investigate the clinical relevance of expression PD-L1, Okamoto and colleagues analyzed tumor samples completely resected from 164 patients with NSCLC by immunohistochemistry.
They report in Annals of Oncology that the expression of PD-L1 was significantly higher in women with tumor samples that men never smokers than smokers in patients with adenocarcinoma than squamous cell carcinoma and those positive for EGFR mutations versus wild-type EGFR .
In multivariate analysis, the presence of EGFR mutations and adenocarcinoma histology were significantly and independently associated with increased expression PD-L1.
According to these results, Okamoto and the team has also shown that PD-L1 expression detected by flow cytometry, was significantly higher in NSCLC cell lines positive for EGFR mutations than in wild-type EGFR .
Moreover, inhibition of EGFR signaling with erlotinib resulted in downregulation of expression in PD-L1 EGFR NSCLC mutation positive cells but not in those of wild-type EGFR "indicating that the expression of PD-L1 is probably dependent on EGFR signaling conferred by activating EGFR mutations," the researchers note.
in terms of prognosis, the investigators found that patients with high (above median) PD-L1 tumor phrase had significantly shorter overall survival than those with low expression, at a median of 55 9 compared to 72.6 months.
and Cox regression analysis confirmed that high expression PD-L1 and advanced stage (II or III) was significantly and independently associated a shorter overall survival.
Taken together, "[t] are data suggest that the therapeutic blocking of the PD1-PD-L1 pathway may improve the effectiveness of treatment EGFR mutation positive NSCLC, "say Okamoto et al.
They conclude that, despite the relatively small sample size and retrospective nature of the study, their results "provide a rationale for future clinical investigations of the PD1-PD-L1 axis as a target for adjuvant chemotherapy in individuals with NSCLC whose resected tumors are found to have a high expression score for PD-L1. "
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