Expression of PD-L1 Is Associated with Inflammatory Microenvironment in Surgical Specimens of Non-Small Cell Lung Cancer.

Ivan Simundza,Vesna Capkun,Josko Juricic,Rina Simundza,Dragan Krnic,Ivan Mario Stanicic,Katarina Vukojevic,Merica Glavina Durdov,Benjamin Benzon

doi:10.3390/jpm11080767

Abstract

The aim of this study was to analyse the expression of PD-L1 in non-small cell lung cancer (NSCLC) and its correlation with immune microenvironment response (IMR), clinic-pathological parameters, and outcome. The sample included 76 male and 32 female patients who underwent surgical resection. The mean age of the males was 66 years, and that of the females was 64 years. Adenocarcinoma (ADC) was diagnosed in 68 (63%) cases, squamous cell carcinoma in 35 (32%) cases, and NSCLC (not otherwise specified) in 5 (5%) cases. Metastatic lymph nodes were found in 38 (36%) patients, 18 with N1 nodes and 20 with N2 nodes. PD-L1 expression was valuated as the percentage of positive cancer cells among all cancer cells. Gender, age, and histologic type were not associated with PD-L1 expression (all p > 0.05). The subtypes of ADC were associated with PD-L1 expression (p = 0.050). The papillary subtype was 4.3 times more common among PD-L1 negative than PD-L1 positive ADC; the solid subtype was 1.9 times more common among PD-L1 positive than PD-L1 negative ADC. IMR was predominantly strong in 19 cases, weak in 36, and absent in 53 cases. The median value of PD-L1 expression in cancer cells was positively correlated with IMR (p = 0.039). PD-L1 expression was not correlated with overall survival (p = 0.643). The patients with strong, inflammatory-like IMR had an average survival time that was 12 months longer than patients with absent/low IMR (LR = 2.8; p = 0.132). In conclusion, the papillary subtype was more commonly PD-L1 negative in comparison with other subtypes of ADC. Positive PD-L1 expression in tumour cells was connected with strong, inflammatory-like IMR. Patients with strong IMR tended to experience better outcomes. Further investigations are needed on larger-scale cohorts to elucidate the insights of this descriptive study.

Highlights

Lung cancer (LC) is the most common cause of cancer death [1]
A possible explanation is that the growth pattern of the solid and acinar subtype has a wider contact with the immune microenvironment than the papillary subtype that grows partially in the alveolar spaces
According to Tancoš et al, PD-L1 is associated with an inflammatory background, measured by CD8 + lymphocytes in the microenvironment [14]

Summary

Introduction

Lung cancer (LC) is the most common cause of cancer death [1]. Classic chemo-radiotherapy for metastatic non-small cell lung cancer (NSCLC) has given way to a new paradigm of personalised therapy. The high mortality rate of LC in Croatia encouraged the adoption of the National Screening program of early detection by low-dose computed tomography, which started in 2020 [1]. One of the goals is to diagnose LC in the early stages when the surgical procedure is the treatment of choice. In the postoperative follow-up, disease-free survival was different among the patients, most of them died of lung cancer. A small biopsy is a source of diagnostic and predictive data and reflexing testing for tyrosine kinase inhibitors, and immune checkpoint molecules

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