Exploratory Research for HIF-1α Overexpression Tumor Antigen in the Activation of Dendritic Cells and the Potent Anti-Tumor Immune Response

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2024 Dec 23

PMID 39713567

Authors

Jinjin Zhao

Haiguang Zhang

Yilin Zhao

Zhiqiang Lin

Fei Lin

Zhiyin Wang

Qingjiang Mo

Guangjian Lu

Guoan Zhao

Guoqiang Wang

Affiliations

Soon will be listed here.

Abstract

Background: Tumor-specific antigens play an important role in dendritic cell (DC)-based immunotherapy. The acquisition of tumor-specific antigens, which are essential for DC-based immunotherapy, poses a significant challenge. This study aimed to explore the efficacy of hypoxia inducible factor-1α (HIF-1α) overexpression tumor antigens in DC-based immunotherapy.

Methods: An HIF-1α over-expression cell line was constructed to prepare HIF-1α overexpression tumor antigens. The expression of CD14, CD40, CD80, CD86, and HLA-DR on the surface of dendritic cells derived from monocytes was assessed using flow cytometry after stimulation with tumor antigens enriched in HIF-1α. T cell proliferation was analyzed by CFSE division following incubation with mature DCs. The apoptotic tumor cells were detected through annexin V/PI staining following coculture with dendritic cells (DCs) stimulated by HIF-1α enriched antigens. The detection of damage-associated molecular pattern molecules (DAMPs) HMGB1 and calreticulin (CALR) was performed using Western blotting.

Results: The results demonstrated that HIF-1α-enriched tumor antigens significantly upregulated the expression of CD40, CD80, CD86, and HLA-DR in DCs compared to normal tumor antigens. Furthermore, co-incubation with HIF-1α-enriched tumor antigen-activated DCs enhanced T cell proliferation and stimulated the T cell-mediated cytotoxicity. Notably, the expression of DAMPs, such as HMGB1 and CALR, was elevated in HIF-1α-enriched tumor antigens.

Conclusion: Our findings demonstrate that tumor antigens enriched with HIF-1α may encompass tumor-specific antigens capable of stimulating DC activation, thereby enhancing T cell proliferation and cytotoxicity. These results provide support for the further advancement of HIF-1α enriched tumor antigens in preclinical and clinical investigations pertaining to tumor treatment.

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