PD‑L1 promotes head and neck squamous cell carcinoma cell growth through mTOR signaling

Zheng, Anyuan; Li, Fen; Chen, Fuhai; Zuo, Jingjing; Wang, Lei; Wang, Yongping; Chen, Shiming; Xiao, Bokui; Tao, Zezhang

doi:10.3892/or.2019.7053

Cited by 23 publications

(16 citation statements)

References 46 publications

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“…In breast cancer, PD-L1 could predict the outcome of patients (41). PD-L1 promoted tumor cell growth through mTOR signaling in head and neck squamous cell carcinoma carcinogenesis cell lines Cal-27 and Fadu (42). Consistent with these findings, the present study revealed that PD-L1 expression was decreased in patients with AML with complete remission compared with that in patients with relapsed or refractory in the 90 samples from patients with AML.…”

Section: Discussionsupporting

confidence: 87%

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Xing

Han

et al. 2020

Oncol Rep

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Acute myeloid leukemia (AML) is a hematological malignancy derived from immature myeloid cells, which have the characteristics of abnormal proliferation and differentiation. Glycolysis has been a popular topic of research in recent years, with increasing uptake and consumption of glucose. The present study aimed to investigate the glycolysis of tumor cells in patients with AML; in particular, how programmed cell death 1 ligand 1 (PD-L1) regulates tumor cells glycolysis using real time PCR (RT-PCR), western blotting and flow cytometry. PD-L1 high expression predicted poor outcome in patients with AML in the public database Gene Expression Profiling Interactive Analysis. PD-L1 expression was decreased in the samples from patients with AML with complete remission compared to that in patients with relapsed or refractory AML. In AML cell lines, glycolysis-associated genes ALDOA, PGK1, LDHA and HK2 were highly expressed in a PD-L1 high-expressed cell line. Overexpressed PD-L1 enhanced glucose consumption and the extracellular acidification rate, accompanied by decreased apoptosis and accumulation of cells in the S phase. In contrast, the apoptosis rate of tumor cells and the percentage of cells in the S phase were significantly increased following PD-L1 knockdown in the THP1 cell line. HK2 and LDHA expression decreased after AML tumor cells were treated with Akt inhibitor or rapamycin. In addition, the PD-L1-overexpressed cell line (PD-L1-OV) MOLM-13 exhibited rapid tumor progression. Glycolysis-associated genes were highly expressed in tumor tissues of PD-L1-OV MOLM-13, with increased Ki67. Based on these findings, PD-L1 may be considered as a suitable marker for prognosis and treatment in the clinical setting.

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Section: Discussionsupporting

confidence: 87%

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Xing

Han

et al. 2020

Oncol Rep

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“…PD‐1 is also considered a marker for exhausted T cells and is often upregulated in CD4 + and CD8 + TILs in various types of cancers 30,31 . CD8 + TILs of human HNSCCs were found to express increased levels of PD‐1 on their surface, 32 and 66% to 79% of patients with SCC had PD‐L1‐positive tumor cells 33–36 . In addition, we previously showed that CD8 + TILs in a mouse SCC model highly expressed PD‐1 and LAG‐3 37 .…”

Section: T Cellsmentioning

confidence: 95%

Tumor immune microenvironment in head and neck cancers

Chen

Krinsky

Woolaver

et al. 2020

Molecular Carcinogenesis

111

114

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Head and neck cancers are a heterogeneous group of tumors that are highly aggressive and collectively represent the sixth most common cancer worldwide.Ninety percent of head and neck cancers are squamous cell carcinomas (HNSCCs).The tumor microenvironment (TME) of HNSCCs consists of many different subsets of cells that infiltrate the tumors and interact with the tumor cells or with each other through various networks. Both innate and adaptive immune cells play a crucial role in mediating immune surveillance and controlling tumor growth. Here, we discuss the different subsets of immune cells and how they contribute to an immunosuppressive TME of HNSCCs. We also briefly summarize recent advances in immunotherapeutic approaches for HNSCC treatment. A better understanding of the multiple factors that play pivotal roles in HNSCC tumorigenesis and tumor progression may help define novel targets to develop more effective immunotherapies for patients with HNSCC.

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“…Interestingly, the present findings also suggest that targeting PDL1 in MUC1-positive tumor-bearing mice inhibited tumor growth and elicited a stronger antitumor effect than that in MUC1-negative tumor-bearing mice. This provides further in vivo evidence of the tumor suppressor function of PDL1 ( 44 – 46 ).…”

Section: Discussionmentioning

confidence: 65%

MUC1‑induced immunosuppression in colon cancer can be reversed by blocking the PD1/PDL1 signaling pathway

et al. 2020

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Mucin1 (MUC1) upregulation in colon cancer has been linked to poor patient outcomes and advanced stage at diagnosis. This is partially due to MUC1-mediated inhibition of T-cell proliferation affecting efficient lysis by cytotoxic lymphocytes, which contributes to escape from immune surveillance. In the present study, human colorectal cancer tissues were collected, and MUC1-positive and MUC1-negative colon cancer mouse models were prepared; subsequently, the number and function of immune cells in tumor tissues were measured using flow cytometry. The present study revealed that MUC1, as a tumor-associated antigen, can recruit more tumor-infiltrating lymphocytes into the tumor microenvironment compared with MUC1-negative colon cancer, but that these cells could not serve antitumor roles. Conversely, the present study demonstrated that MUC1-positive colon cancer attracted more regulatory T cells (Treg cells), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) to the tumor site than MUC1-negative colon cancer. Furthermore, the data suggested that programmed death protein 1 (PD1)-programmed death ligand 1 (PDL1) expression is greater in MUC1-positive colon cancer. Blocking the PD1-PDL1 signaling pathway reduced the percentage of Treg cells, MDSCs and TAMs in the tumor microenvironment, enhanced T-cell cytotoxicity and inhibited tumor growth, prolonging the survival time of MUC1-positive tumor-bearing mice. Therefore, the present study elucidated the role of MUC1 in tumor immune escape and provides a foundation for the application of PDL1 inhibitors to MUC1-positive colon cancer.

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PD‑L1 promotes head and neck squamous cell carcinoma cell growth through mTOR signaling

Cited by 23 publications

References 46 publications

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Tumor immune microenvironment in head and neck cancers

MUC1‑induced immunosuppression in colon cancer can be reversed by blocking the PD1/PDL1 signaling pathway

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