Variation of Programmed Death Ligand 1 Expression After Platinum-based Neoadjuvant Chemotherapy in Lung Cancer

Abstract

The effect of chemotherapy on programmed cell death-ligand 1 (PD-L1) expression has been previously studied in lung cancer, while the results remain controversial. The aim of this study was to investigate the variation of PD-L1 expression after neoadjuvant chemotherapy and explore the association between chemotherapy response, prognosis and the variation of PD-L1 expression in lung cancer patients. A total of 63 lung cancer patients who received platinum-based neoadjuvant chemotherapy and subsequently underwent surgical resection were selected. PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) was assessed by immunohistochemistry using 22C3 monoclonal antibody in these 63 matched lung cancer specimens before and after neoadjuvant chemotherapy. The positivity of PD-L1 on TC changed from 17.5% to 39.7% after neoadjuvant chemotherapy and the positivity of PD-L1 on IC changed from 19.0% to 71.4% after neoadjuvant chemotherapy. The elevation of PD-L1 expression on TC after neoadjuvant chemotherapy was more frequently observed in patients achieving stable disease or progressive disease than in patients achieving partial response ( P =0.026). Patients with elevated PD-L1 expression on TC after neoadjuvant chemotherapy showed a trend to have a shorter progression-free survival than patients without elevated PD-L1 expression on TC, although the difference was not statistically significant in multivariate analysis (hazard ratio=2.38, 95% confidence interval=0.99–5.73, P =0.053). PD-L1 expression can be elevated by chemotherapy in lung cancer. Furthermore, elevation of PD-L1 expression on TC after neoadjuvant chemotherapy was associated with reduced chemotherapy response and inferior progression-free survival in patients with lung cancer.

Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study

“…Therefore, our results should preferentially be considered when using the E1L3N antibody clone. Finally, our results should be interpreted with the caveat that both PD-L1 and PD-1 expressions are variable over time, and although the majority of included patients were CHT-naïve at biopsy, the application of CHT prior to tissue sampling can possibly confound expression patterns (37,53,54). Nevertheless, this study examined a relatively large number of patients in a multicenter setting and we used multiple cut-off values in order to get a clearer insight into the expression pattern and prognostic impact of both PD-L1 and PD-1.…”

Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer

“…In addition, the tumor PD-L1 expression level was shown to be significantly increased by neoadjuvant platinum-based chemotherapy in some patients with NSCLC. 34,35 Thus, the anticipated enhancement of PD-L1 expression by carboplatin and paclitaxel might have led to the preferable efficacy of nivolumab in patients with negative PD-L1 expression at baseline.…”

Is PD-L1 a consistent biomarker for anti-PD-1 therapy? The model of balstilimab in a virally-driven tumor

“…Prior to treatment, 17.4% (11) and 15.9% (10) of patients expressed PD-L1 on tumor and immune cells, respectively. After treatment, 40.0% (25) and 71.4% (45) of patients expressed PD-L1 on tumor and immune cells, respectively [ 6 ]. Second, 65% (28/43) of melanoma patients treated with one cycle of nivolumab therapy exhibited upregulated PD-L1 expression as assessed by RNA-sequencing [ 7 ].…”