Abstract
Conventional chemotherapy for lung cancer exerts anti-tumor effects through cytotoxicity, and through immunologic regulation by reducing specific T cell subsets and inducing the expression of programmed death ligand 1 (PD-L1) on tumor cells. Even though pemetrexed has shown huge potential in combination with other targeted or immune therapies, there is still little information about the values of specific immune checkpoint markers for advanced lung adenocarcinoma treated with pemetrexed. In the present study, a total of 56 patients with advanced lung adenocarcinoma, who received pemetrexed-based chemotherapy, were included retrospectively. Immunohistochemistry was performed to assess PD-L1, programmed death 1 (PD-1), thymidylate synthase, and tumor infiltrating lymphocytes (TILs). In this cohort, the positive expression of PD-L1 and PD-1 were 26.8% and 33.9% respectively. PD-L1, PD-1, and thymidylate synthase expression were not significantly associated with any clinical features, while the expression of both PD-L1 and PD-1 were correlated with Ki-67 expression. Furthermore, the expression of PD-1 was significantly correlated with TILs. The progression-free survival (PFS) in patients with PD-L1+ specimens was significantly longer compared to PD-L1− specimens. Moreover, PD-L1 expression was an independent protective factor for PFS, and the smoking status was an independent risk factor. PD-L1 expression was significantly associated with better prognosis for patients with pemetrexed-based treatment. Our findings suggested that PD-L1 expression might be a favorable prognostic biomarker for pemetrexed-based regimen, which is a rationale for combining immunotherapy with chemotherapy for lung cancer.
Highlights
Lung cancer is the leading cause of cancer-related mortality worldwide, causing more than one million deaths annually [1]
The purpose of the current study is to investigate the possible association between the PD pathway and the prognosis for lung adenocarcinoma patients treated with pemetrexed-based chemotherapy
We found that PDL1 expression was significantly correlated with a longer survival in these patients, indicating that the expression of programmed death ligand 1 (PD-L1) might be a favorable prognosis biomarker for pemetrexed-based therapy, which is a rationale for combining the immunotherapy with chemotherapy for lung cancer
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide, causing more than one million deaths annually [1]. 85% of patients with lung cancer are diagnosed with non-small-cell lung cancer (NSCLC), while 80% are diagnosed with advanced stages [2, 3]. Conventional cytotoxic chemotherapy, which includes platinum (cisplatin or carboplatin) and a non-platinum drug (pemetrexed, gemcitabine, etc.), has been used as the standard treatment in these patients [4]. The great progress has recently been made in targeted therapies and immunotherapies, platinum-based doublet chemotherapy still remains the foundation for the majority of patients with advanced lung cancer [4]. Chemotherapy has been shown to regulate the immune system and overcome the resistance to targeted therapy, indicting its potential for coordination with other therapies [4]. The predictive biomarkers for chemotherapy and its combination strategy remain unknown
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