Abstract
Programmed death ligand 1 (PD-L1) is an immune checkpoint with a role in cancer-related immune evasion. It is a target for cancer immunotherapy and its expression is detected for the use of some immune checkpoint inhibitors in advanced non-small cell lung cancer patients (NSCLC). Vimentin is a key component of the epithelial-to-mesenchymal transition phenotype. Its expression has negative prognostic effects in NSCLC. In this study, we retrospectively evaluated PD-L1 and vimentin expression in tumor cells, immune infiltrate and PD-L1 positive immune infiltrate via immunohistochemistry in tissue samples from resected non-metastatic NSCLC patients. We explored the interplay between PD-L1 and vimentin expression through Spearman’s correlation test. We performed univariate analysis through the Cox models for demographic and clinico-pathological variables, and also for dichotomized biomarkers, i.e., PD-L1 and vimentin in tumor cells, both with 1 and 50% cutoffs. We used Kaplan-Meier method to estimate the overall survival, comparing both vimentin and PD-L1 positive patients with all the others. We found a weak positive correlation between PD-L1 and vimentin expressions in tumor cells (r = 0.25; p = 0.001). We also observed a statistically not significant trend towards a shorter overall survival in patients with both PD-L1 and vimentin expression >1% (HR = 1.36; 95% CI: 0.96–1.93, p = 0.087). In conclusion, these findings suggest that interplay between PD-L1 and vimentin may exist in non-metastatic NSCLC patients and the positivity of both markers in tumor tissue is associated with a trend towards a worse prognosis.
Highlights
Lung cancer is still the leading cause of mortality by cancer, despite recent therapeutic advances
We explored a potential role of immune infiltrate in tumor tissue and analyzed the prognostic impact of these combined markers
Vimentin expression is not directly involved in the treatment of this neoplasm, but it has a key role in the Epithelial–mesenchymal transition (EMT) process, which seems to be involved in resistance to various cancer treatments
Summary
Lung cancer is still the leading cause of mortality by cancer, despite recent therapeutic advances. Post-surgical adjuvant platinum-based chemotherapy is used to achieve a modest improvement of around 5% in 5-year overall survival (OS) in patients who underwent complete resection for stage II and IIIA (Pignon et al, 2008) It can be considered in those patients who underwent resection for stage IB NSCLC if the primary tumor is greater than 4 cm. For unresectable stage IIIA or IIIB disease the treatment of choice is represented by concurrent chemoradiation therapy or, as an alternative, sequential chemotherapy followed by definitive radiotherapy (Postmus et al, 2017) In both cases, concurrent or sequential therapy, a consolidation with durvalumab, an immune checkpoint inhibitor (ICI), is approved according to the results of PACIFIC trial (Antonia et al, 2017). ICIs are currently being evaluated as neoadjuvant/adjuvant therapy in combination with standard treatments (Mielgo-Rubio et al, 2020)
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