Tumor necrosis correlates with PD-L1 and PD-1 expression in lung adenocarcinoma

Reiniger, Lilla; Téglási, Vanda; Pipek, Orsolya; Rojkó, Lívia; Glasz, Tibor; Vágvölgyi, Attila; Kovalszky, Ilona; Gyulai, Márton; Lohinai, Zoltán; Rásó, Erzsébet; Tı́már, József; Döme, Balázs; Szállási, Zoltán; Moldvay, Judit

doi:10.1080/0284186x.2019.1598575

Cited by 25 publications

(21 citation statements)

References 46 publications

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“…Another interesting finding in the current study is the correlation of tumor necrosis and PD-L1 expression. These are in accordance to other studies that showed tumors with higher PD-L1 expression with a greater tendency to necrosis, a more aggressive tumor phenotype and higher proliferation rate ( 39 , 40 ).…”

Section: Discussionsupporting

confidence: 93%

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Alves

Borges²,

Kimberly

et al. 2021

Front. Oncol.

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BackgroundGlycogen Synthase Kinase-3 beta (GSK-3β) regulates diverse cell functions including metabolic activity, signaling and structural proteins. GSK-3β phosphorylates target pro-oncogenes and regulates programmed cell death-ligand 1 (PD-L1). This study investigated the correlation between GSK-3β expression and clinically relevant molecular features of lung adenocarcinoma (PDL1 score, PTEN expression and driver mutations).MethodsWe evaluated 95 lung cancer specimens from biopsies and surgical resections. Immunohistochemistry was performed to analyze the expression of GSK-3β, PTEN, and PDL1. Epidemiological data, molecular characteristics and staging were evaluated from medical records. The histologic classification was performed by an experienced pulmonary pathologist.ResultsMost patients were female (52.6%) and the majority had a positive smoking history. The median age was 68.3 years, with individuals over 60 years accounting for 82.1%. The predominant histological subtype was adenocarcinoma (69.5%), followed by squamous cell carcinoma (20.0%). GSK-3β expression in tumors was cytoplasmic with a dotted pattern and perinuclear concentration, with associated membranous staining. Seven (7.3%) tumors had associated nuclear expression localization. Seventy-seven patients (81.1%) had advanced clinical-stage tumors. GSK-3β was positive in 75 tumors (78%) and GSK3-positive tumors tended to be diagnosed at advanced stages. Among stage III/IV tumors, 84% showed GSK3 positivity (p= 0.007). We identified a statistically significant association between GSK-3β and PTEN in the qualitative analysis (p 0.021); and when comparing PTEN to GSK-3β intensity 2+ (p 0.001) or 3+ expression (> 50%) – p 0.013. GSK-3β positive tumors with a high histological score had a worse overall survival.ConclusionWe identified the histological patterns of GSK-3β expression and evaluated its potential as marker for overall survival, establishing a simple histological score to measure the evaluated status in resected tissues. The use of GSK-3β expression as an immune response biomarker remains a challenge. Future studies will seek to explain the role of its interaction with PTEN.

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Section: Discussionsupporting

confidence: 93%

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Alves

Borges²,

Kimberly

et al. 2021

Front. Oncol.

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“…The elevated expression of programmed cell death ligand 1 (PD-L1) has been demonstrated in KRAS-mutant cells, and it was also shown that ERK activation mediates the upregulation of PD-L1 by KRAS mutations [ 60 ]. On the contrary, Reiniger et al did not find significant relations between PD-L1 expression and KRAS status in LADC [ 61 ]. It was also reported that pembrolizumab (a PD-1 inhibitor) or an ERK inhibitor might prevent CD3+ T cells becoming apoptotic by recovering tumor immunity thus preventing immune escape [ 62 ].…”

Section: Predictive Role Of Kras Mutationsmentioning

confidence: 99%

Current therapy of KRAS-mutant lung cancer

Ghimessy

Radeczky

László

et al. 2020

Cancer Metastasis Rev

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KRAS mutations are the most frequent gain-of-function alterations in patients with lung adenocarcinoma (LADC) in the Western world. Although they have been identified decades ago, prior efforts to target KRAS signaling with single-agent therapeutic approaches such as farnesyl transferase inhibitors, prenylation inhibition, impairment of KRAS downstream signaling, and synthetic lethality screens have been unsuccessful. Moreover, the role of KRAS oncogene in LADC is still not fully understood, and its prognostic and predictive impact with regards to the standard of care therapy remains controversial. Of note, KRASrelated studies that included general non-small cell lung cancer (NSCLC) population instead of LADC patients should be very carefully evaluated. Recently, however, comprehensive genomic profiling and wide-spectrum analysis of other co-occurring genetic alterations have identified unique therapeutic vulnerabilities. Novel targeted agents such as the covalent KRAS G12C inhibitors or the recently proposed combinatory approaches are some examples which may allow a tailored treatment for LADC patients harboring KRAS mutations. This review summarizes the current knowledge about the therapeutic approaches of KRASmutated LADC and provides an update on the most recent advances in KRAS-targeted anti-cancer strategies, with a focus on potential clinical implications.

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“…Pembrolizumab has been approved as rst-line treatment for advanced PD-L1 positive NSCLC patients [29]. In our study, we found that high expression of PD-L1 was detected in 44.6% (29/65) cases of cavitary LUAD, signi cantly increased, compared to 20% (6/30) cases of noncavitary lung cancer, which demonstrated tumor necrosis correlates with higher PD-L1 expression in the LUAD [30]. Moreover, high expression of PD-L1 was correlated with high TNM stage, and could predict poor prognosis of patients with cavitary LUAD.…”

Section: Discussionmentioning

confidence: 53%

High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

Liu

Yang

et al. 2020

Preprint

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Objective Solitary cavitary lung cancer is one of the rare types of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma and immunotherapy remains unknown. We aimed to assess programmed cell death ligand-1(PD-L1) expression and CD8-positive (CD8+) tumor infiltrating lymphocytes (TILs) density, and evaluate their prognostic significance of patients with cavitary lung adenocarcinoma (LUAD). Methods 65 patients diagnosed as solitary cavitary LUAD were included in this study, 30 cases of noncavitary LUAD patients were collected as controls, and their specimens from surgery or biopsy were obtained. Expression of PD-L1 protein and CD8+ TILs were detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlations of PD-L1 expression and clinicopathological features, including overall survival in cavitary LUAD patients was evaluated based on the follow-up data. Results Overexpression of PD-L1 protein was detected in the tumor tissues of cavitary LUAD patients compared to the noncavitary LUAD controls. PD-L1 expression level was significantly related to the lymph node (P = 0.001), TNM stage (P = 0.024), and CD8+ TIL status (rs= -0.272, P = 0.025). High PD-L1 expression predicted high mortality rate (P < 0.001), but CD8+ TIL group showed better survival in cavitary LUAD patients (P = 0.011). This phenotype with high PD-L1 expression and low CD8 + TIL predicted poorer overall survival of the patients with cavitary LUAD, compared to the other phenotypes. Moreover, CD8+ TIL was an independent good prognosis factor. Conclusion We firstly demonstrated that PD-L1 is upregulated in the cavitary LUAD patients, and high expression of PD-L1 negatively correlated with CD8 T cell infiltrating status. High PD-L1 expression and low CD8 + TIL can predict poorer overall survival of the patients with cavitary LUAD.

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Tumor necrosis correlates with PD-L1 and PD-1 expression in lung adenocarcinoma

Cited by 25 publications

References 46 publications

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Current therapy of KRAS-mutant lung cancer

High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

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