The association of CD8+ T-cell infiltration and PD-L1 expression with prognosis of Chinese pulmonary large cell neuroendocrine carcinoma.

Abstract

e21003 Background: Pulmonary large cell neuroendocrine carcinoma (LCNCE) is a high-grade neuroendocrine tumor with poor prognosis. The genomic profile and immune feature of LCNEC have been reported in many studies. However, the relationship between immune microenvironment and the prognosis of LCNEC patients is poorly understood. Our study was aimed to examine the infiltration of CD8+ T cell and PD-L1+ cells in LCNEC patients, and explore whether CD8+T cell and PD-L1+ cells are related to LCNEC patients’ prognosis. Methods: 37 eligible LCNEC patients (stage I-III) with received the treatment of surgical operation (27 among 37 patients underwent adjuvant radiochemotherapy) were included, tumor tissues were collected from the first medical center of Chinese PLA General Hospital. Multiplex immunohistochemistry (Multi IHC) was performed using the antibodies of CD8 and PD-L1. The univariate and multivariate cox proportional hazards analyses were used to assess the association between the abundance of CD8+T cell and PD-L1+ cells with the clinical outcome of LCNEC patients. Results: Patients were divided into high and low group using the median positive percentage of CD8 or PD-L1 as cutoff. The univariate analysis showed that patients with stromal high CD8+ T cell infiltration or stage I had significantly longer disease free survival (DFS) (CD8, p = 0.03; stage I, p = 0.036), and patients with high PD-L1 expression in stroma region, I stage, adjvant radiochemotherapy had notably increased overall survival (OS) (p = 0.049, p = 0.031, p = 0.023, respectively). However, the infiltration of CD8+ T cell or PD-L1 expression in total or tumor region had no correlation with survival of LCNEC patients. Furthermore, multivariate analysis demonstrated that low CD8+ T cell density in stroma region was an independent risk factor for PFS (p = 0.03), advanced TNM stage (II-III stage, p = 0.0009) and low stromal PD-L1 expression were independent risk factors for OS (p = 0.013). Conclusions: High infiltration of CD8+ T cell or PD-L1+ cell in stroma region were independent good prognosis factors of LCNEC patients. However, these findings need a larger LCNEC cohort to validate.