Several groups have reported that programmed death-1 (PD-1) ligand 1 (PD-L1) overexpression on tumor cells predicts a poor prognosis in patients with non-small cell lung cancer (NSCLC). Although recent studies have shown that PD-L1 overexpression on tumor cells predicts for improved clinical outcome in NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy, PD-L1 low/negative tumors also benefit from anti-PD-1/PD-L1 immunotherapy. These findings suggest that study on multiple immune parameters should be considered. We recently reported that the overexpression of PD-L1 in tumor predicted a poor prognosis while overexpression of NK cell activating ligand MICA/B predicted improved clinical outcome in patients with resected NSCLC. It is well known that both T cell- and NK cell-mediated tumor recognitions are influenced by HLA class I molecules, however, the roles of HLA class I molecules are different between T cells and NK cells; HLA class I/T cell receptor immune synapse induces antigen-specific cytotoxicity by T cell, while HLA class I/killer cell immunoglobulin-like receptor synapse attenuates NK cell-mediated cytotoxicity. Here, we assessed the multiple immune parameters (PD-L1, MICA/B, and HLA class I) in NSCLC tissues to assess the prognostic factors in patients with resected NSCLC.
We examined resected tumor tissues from 91 patients with pathological stage IA-IIIA NSCLC using immunohistochemical reaction for the expression of PD-L1, MICA/B, and HLA class I then assessed whether the multiple immune parameters impact on the clinical outcome of patients with NSCLC.
PD-L1low/MICA/Bhigh tumors have an excellent disease free survival time (DFS) compared with PD-L1low/MICA/Blow (p=0.010 by log-rank test) or PD-L1high (p
Multiple immune parameters using the expression status of MICA/B and PD-L1 or HLA class I on tumor cells are useful prognostic factors for NSCLC. We should have more concerns to NK cell-mediated tumor elimination in anti-PD-1/PD-L1 immunotherapy.
Clinical trial identification
Legal entity responsible for the study
Okita Riki, Kawasaki Medical School
Japan Society for the Promotion of Science (JSPS) Kakenhi Grant (25462189 and 16K10696) (to R.O)
M. Nakata: Research funding from Kyowa Kirin, Taiho Pharma, and Ono Pharma. The sponsors had no control over the interpretation, writing, or publication of this work. All other authors have declared no conflicts of interest.