PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival

Aberrant vascular network is a hallmark of cancer. However, the role of vascular endothelial cells (VECs)-expressing PD-L1 in tumor immune microenvironment and antiangiogenic therapy remains unclear. In this study, we used the specimens of cancer patients for immunohistochemical staining to observe the number of PD-L1 + CD34 + VECs and infiltrated immune cells inside tumor specimens. Immunofluorescence staining and flow cytometry were performed to observe the infiltration of CD8 + T cells and FoxP3 + T cells in tumor tissues. Here, we found that PD-L1 expression on VECs determined CD8 + T cells', FoxP3 + T cells' infiltration, and the prognosis of patients with lung adenocarcinoma. Anlotinib downregulated PD-L1 expression on VECs through the inactivation of AKT pathway, thereby improving the ratio of CD8/FoxP3 inside tumor and remolding the immune microenvironment. In conclusion, our results demonstrate that PD-L1 high expression on VECs inhibits the infiltration of CD8 + T cells, whereas promotes the aggregation of FoxP3 + T cells into tumor tissues, thus becoming an "immunosuppressive barrier". Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth.

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“…HIF-1α and VEGFA expression were scored by the H-score system, respectively. H score calculation method is based on previous literature 15 .…”

Section: Evaluation Of the Percent Of Pd-l1 + Blood Vessels And The Pmentioning

confidence: 99%

anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells

et al. 2020

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“…VEGFA, an important member of vascular endothelial growth factor signaling pathway, mediates the tumoral angiogenesis, and results in the progression and metastasis of NSCLC (41,42). Besides, Liu et al (43) demonstrated that the co-expression of VEGFA and PD-L1 exhibited a worst overall survival in patients with resected LUAD, indicating the potential complicated interaction between VEGFA expression and immune checkpoint inhibitor therapy. The critical role TGFβ/BMP signaling pathway played in tumor cell growth, stemness, epithelial-mesenchymal transition, invasion, and migration in triple-negative breast cancer has also been published (44,45).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a 12-Gene Immune Relevant Prognostic Signature for Lung Adenocarcinoma Through Machine Learning Strategies

Zhan

et al. 2020

Front. Oncol.

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Background: Although immunotherapy with checkpoint inhibitors is changing the face of lung adenocarcinoma (LUAD) treatments, only limited patients could benefit from it. Therefore, we aimed to develop an immune-relevant-gene-based signature to predict LUAD patients' prognosis and to characterize their tumor microenvironment thus guiding therapeutic strategy. Methods and Materials: Gene expression data of LUAD patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were systematically analyzed. We performed Cox regression and random survival forest algorithm to identify immune-relevant genes with potential prognostic value. A risk score formula was then established by integrating these selected genes and patients were classified into high-and low-risk score group. Differentially expressed genes, infiltration level of immune cells, and several immune-associated molecules were further compared across the two groups. Results: Nine hundred and fifty-four LUAD patients were enrolled in this study. After implementing the 2-steps machine learning screening methods, 12 immune-relevant genes were finally selected into the risk-score formula and the patients in high-risk group had significantly worse overall survival (HR = 10.6, 95%CI = 3.21-34.95, P < 0.001). We also found the distinct immune infiltration patterns in the two groups that several immune cells like cytotoxic cells and immune checkpoint molecules were significantly enriched and upregulated in patients from the high-risk group. These findings were further validated in two independent LUAD cohorts. Conclusion: Our risk score formula could serve as a powerful and accurate tool for predicting survival of LUAD patients and may facilitate clinicians to choose the optimal therapeutic regimen more precisely.

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“…H‐score > 100 was identified as a VEGFC high expression case. According to previous studies, PD‐L1 cutoff value was set at 100, ie. H‐score >100 was considered to be a PD‐L1 high expression case.…”

Section: Methodsmentioning

confidence: 99%

Clinical importance of VEGFC and PD‐L1 co‐expression in lung adenocarcinoma patients

et al. 2020

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Background: Vascular endothelial growth factor C (VEGFC), an activator of lymphangiogenesis, is newly identified as an immunomodulator which can regulate the immune system so that tumor cells more easily escape immune surveillance. Evidence has shown programmed cell death-ligand 1 (PD-L1) can also suppress the immune response. Nevertheless, the clinical significance of coexpression of VEGFC and PD-L1 for predicting outcomes in patients with lung adenocarcinoma has not yet been determined. Methods: A total of 114 patients with lung adenocarcinoma who underwent surgeries at were retrospectively reviewed. Tissue specimens were collected for immunohistochemistry of VEGFC and PD-L1 which were analyzed with an H-score system. Results: In this study, 57 (50.0%) and 47 (41.2%) patients were classified as VEGFC high expression and PD-L1 high expression. Co-expression was observed in 33 (28.9%) patients. In addition, a positive correlation was found between VEGFC and PD-L1 (P = 0.0398, r = 0.1937). In a univariate analysis, both progression-free survival (PFS) and overall survival (OS) were significantly worse in the VEGFC high expression group and the PD-L1 high expression group, respectively. Furthermore, VEGFC/PD-L1 co-expression showed a worse OS (P = 0.03) and PFS survival (P = 0.01) than the other groups. Conclusions: Taken together, these results indicate that VEGFC/PD-L1 coexpression can forecast both poor OS and PFS in patients with resected lung adenocarcinoma. Co-expression of VEGFC and PD-L1 may serve as a significant prognostic factor for patients with lung adenocarcinoma. Key pointsVEGFC/PD-L1 co-expression forecasts poor survival in patients with resected lung adenocarcinoma. VEGFC/PD-L1 co-expression may be used as a prognostic indicator and provide the theoretical possibility to screen the optimal population with a combination of anti-VEGFC and anti-PD-L1 therapy in the clinical treatment.

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PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival

Cited by 15 publications

References 35 publications

anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells

anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells

Development and Validation of a 12-Gene Immune Relevant Prognostic Signature for Lung Adenocarcinoma Through Machine Learning Strategies

Clinical importance of VEGFC and PD‐L1 co‐expression in lung adenocarcinoma patients

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