Association of PD-L1 expression with tumor infiltrating immune cells and mutation burden in the high grade neuroendocrine carcinoma of the lung.

Abstract

8564 Background: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high grade neuroendocrine carcinoma of the lung and remain among the most fatal malignancies. Programmed death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable for specific immunotherapy. We retrospectively investigated PD-L1 expression in tumor cells (TC) and tumor infiltrating immune cells (IC) and correlated this with mutation burden and clinical outcome. Methods: A total of 192 patients with LCNEC (n = 72) and SCLC (n = 120) were explored. PD-L1 expression was scored by immunohistochemistry in TC and IC. We used the Ion AmpliSeq Comprehensive Cancer Panel to identify mutation in all exons in 409 cancer-related genes. Results: The overall prevalence of PD-L1 expression on TC was 15.1 % (29/192). No significant difference was observed between LCNEC and SCLC (16.7% vs. 14.2%, p = 0.365). Tumor-infiltrating IC and PD-L1 positive immune cells (IC) were observed in 34.4% (66/192) and 31.3% (60/192), respectively. The prevalence of tumor-infiltrating IC and PD-L1 expression on IC were significantly higher in LCNEC compared to SCLC (57.6% vs. 23.3%, p < .001; 45.8% vs. 22.5%, p = .001, respectively). Tumor-infiltrating IC and PD-L1 expression on IC were correlated with higher nonsynonymous mutational load (p = 0.048 and 0.038, respectively). Tumor-infiltrating immune cells (median 11.3 vs. 6.8 months, p = 0.005), and its correlated PD-L1 expression on IC (median 11.3 vs. 7.0 months, p = 0.024) were related with better progression free survival. There was no relevance between biomarker status and overall survival. Conclusions: These findings suggest that the PD-1/PD-L1 pathway is activated in a fraction of HGNEC of lung with correlating higher mutational burden. Further studies are needed to determine the PD-L1 expression and correlated clinical features to refine role of anti-PD1 treatments in these patient population.