Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non–Small-Cell Lung Cancer: Results from a Large and Pooled Microarray Database

Deng, Lei; Győrffy, Balázs; Na, Feifei; Chen, Baoqing; Lan, Jie; Xue, Jianxin; Zhou, Lin; Lü, You

doi:10.1097/jto.0000000000000550

Cited by 41 publications

(38 citation statements)

References 38 publications

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“…Calles et al suggested that PD‐L1 expression was induced by smoking in KRAS mutant NSCLC . Deng et al reported that those who had smoked had elevated gene expression of PD‐L1 compared with those who never smoked . These results were consistent with ours.…”

Section: Discussionsupporting

confidence: 90%

High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild‐type epidermal growth‐factor receptor cases

Mori

Motoi

Ninomiya

et al. 2016

Pathology International

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A clinical implication of programmed cell death 1 ligand 1 (PD-L1) expression in lung adenocarcinoma has not been well established. We evaluated PD-L1 expression immunohistochemically on 296 surgically resected lung adenocarcinomas to investigate a clinical implication of PD-L1 expression especially in terms of smoking history and epidermal growth-factor receptor (EGFR) mutation status. Patients were classified into high- and low-PD-L1 expression groups. The high-expression group (n = 107) showed a significantly higher proportion of smokers and poor differentiation compared with the low-expression group (n = 189). Survival analysis showed that the prognosis of the high-expression group was worse in overall survival than that of the low-expression group (3-year overall survival 85 vs. 94%, P = 0.005). Stratified survival analyses showed that the prognoses of the high-expression group were worse than those of the low-expression group in both strata of smokers and wild-type EGFR (P = 0.009 and P = 0.007, respectively). We found that high PD-L1 expression was a poor prognostic factor in the smokers or the patients with wild-type EGFR, whereas it was not the case in those who never smoked or those with EGFR mutation, implying the importance of adenocarcinoma driver mutations and etiology.

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Section: Discussionsupporting

confidence: 90%

High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild‐type epidermal growth‐factor receptor cases

Mori

Motoi

Ninomiya

et al. 2016

Pathology International

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“…Mixed findings have been reported regarding the role of PD‐1+ TILs that varied depending on tumor type. Indeed, a favorable role has been revealed for PD‐1+ TILs in ovarian, pancreatic, colorectal cancers, whereas in prostate, renal and lung cancers, and melanoma high PD‐1 expression was associated with worse survival rates . Of note, the prognostic role of this immune marker was tumor compartment‐dependent in our work.…”

Section: Discussionsupporting

confidence: 52%

The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

et al. 2017

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We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD-L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD-1, CD8 and PD-L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of HPV16 DNA/p16 status. The median follow-up was 48 months (range: 4-100). The 2-year-OS was 84.1% for the entire cohort. High PD-1 and PD-L1 expression were more common in patients with positive HPV16 DNA (p < 0.001 and p = 0.008, respectively) and high infiltration by CD8+ TILs (p < 0.001 for both markers). High PD-L1 expression correlated with superior OS (p = 0.025), LPFS (p = 0.047) and DMFS (p = 0.048) in multivariable analysis, whereas no significance could be demonstrated for PD-1. Patients with CD8 /PD-L1 expression had favorable outcome (p < 0.001 for all endpoints) compared to other groups. We validated the superior OS data on CD8 /PD-L1 using the Cancer Genome Atlas TCGA dataset (n = 518; p = 0.032). High PD-L1 expression was a favorable prognostic marker in HPV16-negative but not HPV16-positive patients. In conclusion, HPV-positive tumors showed higher expression of immune markers. PD-L1 expression constitutes an independent prognostic marker in SCCHN patients post-adjuvant CRT. In conjunction with CD8 status, these data provide an important insight on the immune contexture of SCCHN and are directly relevant for future treatment stratification with PD-1/PD-L1 immune checkpoint inhibitors to complement CRT.

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“…Given that evidence of significant and durable anti-tumor efficacy has been demonstrated using PD-1/PD-L1 inhibitors in several NSCLC clinical trials [5–9], numerous efforts are ongoing to identify determinants of response, including PD-L1 expression [5–9, 22, 23], CD8+ TIL [24], smoking status [7–9] and mutation/neoantigen burden [25]. …”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC)

Jiang

Su²,

Zhang³

et al. 2017

Oncotarget

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In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC.Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization.43.1% of NSCLC patients had PD-L1 positive staining on ≥ 5% tumor cells (TC). Furthermore, dual color immunofluorescence revealed that the majority of PD-L1/CD8 dual positive tumor infiltrating lymphocytes (TIL) had infiltrated into the tumor core. Finally, combined analysis of all eight biomarkers showed that tumor PD-L1 positivity overlapped with known alterations in NSCLC oncogenic tumor drivers in 26% of SCC and 76% of AD samples.Our illustration of the eight biomarkers’ overlap provides an intuitive overview of NSCLC for personalized therapeutic strategies using anti-PD-1/PD-L1 immune therapies, either as single agents, or in combination with targeted therapies. For the first time, we also report that PD-L1 and CD8 dual positive TILs are predominantly located within the tumor core.

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Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non–Small-Cell Lung Cancer: Results from a Large and Pooled Microarray Database

Abstract: In this study with large number of patients, PDCD1 and CTLA-4 expression is significantly higher in squamous carcinoma and current/former smokers. Higher expression of CTLA-4, but not PDCD1 predicts worse survival.

Cited by 41 publications

References 38 publications

High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild‐type epidermal growth‐factor receptor cases

High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild‐type epidermal growth‐factor receptor cases

The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC)

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