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

2021 ◽  
Vol 11 (8) ◽  
pp. 767
Author(s):  
Ivan Simundza ◽  
Dragan Krnic ◽  
Josko Juricic ◽  
Benjamin Benzon ◽  
Rina Simundza ◽  
...  

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.

2015 ◽  
Vol 10 (2) ◽  
pp. 126-130
Author(s):  
Yong Tian ◽  
Cong Chen ◽  
Yu Zhang ◽  
Zhen Zhang ◽  
Haiyan Xie

2021 ◽  
Vol 22 (11) ◽  
pp. 5649
Author(s):  
Yi-Chun Chao ◽  
Kang-Yun Lee ◽  
Sheng-Ming Wu ◽  
Deng-Yu Kuo ◽  
Pei-Wei Shueng ◽  
...  

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.


BioFactors ◽  
2019 ◽  
Vol 45 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Lin Zhu ◽  
Feng Xue ◽  
Ying Cui ◽  
Shanshan Liu ◽  
Gen Li ◽  
...  

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