Abstract
Programmed cell death 1 (PD-1) receptor–ligand interaction is a major pathway that is often hijacked by tumors to suppress immune control. Immunoscore (IS), a combinational index of CD3 and CD8 tumor-infiltrating lymphocyte (TIL) density in the tumor’s center and invasive margin, is a new prognostic tool suggested to be superior to conventional tumor-staging methods in various tumors. This retrospective study aimed to investigate the prevalence and prognostic roles of PD-ligand 1 (PD-L1) expression and IS in non-small cell lung cancer (NSCLC) patients receiving adjuvant chemotherapy. PD-L1 expression and TIL density were evaluated by immunohistochemical analysis in 36 patients with stage II and III NSCLC. Tumors with staining in over 1% of their cells were scored as positive for PD-L1 expression, and we determined the median number of CD3- and CD8-positive TILs as the cutoff point for TIL density. To determine IS, each patient was given a binary score (0 for low and 1 for high) for CD3 and CD8 density in both the tumor center and invasive margin region. PD-L1 expression in tumor cells was observed in 61.1% (22/36) of patients. PD-L1 expression was significantly associated with high IS, and highest IS tended to have a favorable disease-free survival.
Highlights
Lung cancer is the leading cause of death due to cancer worldwide [1]
Immune checkpoint blockade with monoclonal antibodies has recently emerged as a new therapeutic strategy in several malignancies, the role of programed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) density in non-small cell lung cancer (NSCLC) patients receiving adjuvant chemotherapy remains largely unknown
We found a positive correlation between PD-L1 expression and IS, and high IS tended to be associated with favorable DFS
Summary
Lung cancer is the leading cause of death due to cancer worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancer cases, and the most effective treatment for NSCLC is surgical resection [2]. Its ligand, programed cell death-ligand 1 (PD-L1), is frequently overexpressed in many types of human cancer [6]. Recent clinical trials have indicated that the inhibition of this pathway with anti-PD-1/PD-L1 antibodies exerts a promising antitumor effect against several human malignancies, www.impactjournals.com/oncotarget including NSCLC, melanoma, and renal cell cancer [8,9,10,11,12,13,14]. Preliminary observations of patients with recurrent cancers have indicated that clinical responses to immune checkpoint blockers are associated with elevated tumor levels of immune inhibitory signals, such as PD-L1, CTLA-4 and with increased numbers of tumor-infiltrating lymphocytes (TILs) [6, 15,16,17]
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