Dataset Information

Anti-CD47 treatment enhances anti-tumor T-cell immunity and improves immunosuppressive environment in head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is considered as an immunosuppressive disease, with impaired tumor-infiltrating T lymphocytes and increased suppressive immune cells. The efficacy of CD47 antibodies in immune checkpoint therapy is not clearly understood in HNSCC. In this study, human tissue microarrays and immunocompetent transgenic mouse models were used to explore the expression of CD47 and the use of CD47 antibodies in HNSCC. We identified overexpression of CD47 in HNSCC as compared with the control normal human tissue and also in HNSCC mouse models. The expression of CD47 also correlated with clinicopathological parameters as well as outcome. Furthermore, inhibition of CD47 delayed tumor growth and improved tumor microenvironment by stimulating effector T cells and decreasing suppressive immune cells and regulating the function of CD11b⁺ Ly6G⁺ MDSC. Our data suggest that CD47 blockade may be a potential immunotherapeutic target in human HNSCC.

SUBMITTER: Wu L

PROVIDER: S-EPMC5889284 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anti-CD47 treatment enhances anti-tumor T-cell immunity and improves immunosuppressive environment in head and neck squamous cell carcinoma.

Wu Lei L Yu Guang-Tao GT Deng Wei-Wei WW Mao Liang L Yang Lei-Lei LL Ma Si-Rui SR Bu Lin-Lin LL Kulkarni Ashok B AB Zhang Wen-Feng WF Zhang Lu L Sun Zhi-Jun ZJ

Oncoimmunology 20180313 4

Head and neck squamous cell carcinoma (HNSCC) is considered as an immunosuppressive disease, with impaired tumor-infiltrating T lymphocytes and increased suppressive immune cells. The efficacy of CD47 antibodies in immune checkpoint therapy is not clearly understood in HNSCC. In this study, human tissue microarrays and immunocompetent transgenic mouse models were used to explore the expression of CD47 and the use of CD47 antibodies in HNSCC. We identified overexpression of CD47 in HNSCC as compa ...[more]

PMID: 29632717

Similar Datasets

Project description:Background:Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. Methods:Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1?, TNF-?, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey's honest significance test (?=0.05). Results:Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions:These results suggest different patients' HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.

Dataset Information

Anti-CD47 treatment enhances anti-tumor T-cell immunity and improves immunosuppressive environment in head and neck squamous cell carcinoma.

Publications

Anti-CD47 treatment enhances anti-tumor T-cell immunity and improves immunosuppressive environment in head and neck squamous cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets