한빛사논문
- 조회134
Chanju Lee1,2, Dahee Yu1, Hyung-Seok Kim1, Ki Sun Kim1, Chi Young Chang1, Hee Jung Yoon2, Su Bin Won1, Dae Yeon Kim1, Eun Ah Goh1, Yong Sun Lee1, Jong-Bae Park1, Sang Soo Kim3, and Eun Jung Park1,2*
1Department of Cancer Biomedical Science,
2Immuno-oncology Branch, 3Radiological Science Branch, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si Gyeonggi-do, 10408, Republic of Korea
Correspondence to: Eun Jung Park
Abstract
Galectin-9 is a multifaceted regulator of various pathophysiological processes that exerts positive or negative effects in a context-dependent manner. Here, we elucidated the distinctive functional properties of galectin-9 on myeloid cells within the brain tumor microenvironment. Galectin-9-expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared to the contralateral hemisphere in an intracranial mouse brain tumor model. Galectin-9 was highly expressed in microglia and macrophages in tumor-infiltrating cells. In primary glia, both the expression and secretion of galectin-9 were influenced by tumors. Analysis of a human glioblastoma bulk RNA-sequencing dataset and a single-cell RNA-sequencing dataset from a murine glioma model revealed a correlation between galectin-9 expression and glial cell activation. Notably, the galectin-9high microglial subset was functionally distinct from the galectin-9neg/low subset in the brain tumor microenvironment. Galectin-9high microglia exhibited properties of inflammatory activation and higher rates of cell death, whereas galectin-9neg/low microglia displayed a superior phagocytic ability against brain tumor cells. Blockade of galectin-9 suppressed tumor growth and altered the activity of glial and T cells in a mouse glioma model. Additionally, glial galectin-9 expression was regulated by Hif-2α in the hypoxic brain tumor microenvironment. Myeloid-specific Hif-2α deficiency led to attenuated tumor progression. Together, these findings reveal that galectin-9 on myeloid cells is an immunoregulator and putative therapeutic target in brain tumors.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-09-05)
- 국내 연구진
- 의약학 > 의약학 기타
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