2. Academic Validation
  3. Manganese improves CD8+ T cell recruitment via cGAS-STING in hepatocellular carcinoma

Manganese improves CD8+ T cell recruitment via cGAS-STING in hepatocellular carcinoma

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113591. doi: 10.1016/j.intimp.2024.113591.
Chunxue Fu 1,  Hanrui Guo 2,  Meiling Wang 3,  Caiya Ni 1,  Xiangwei Wu 1,  Xueling Chen 1,  Jun Hou 4,  Lianghai Wang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital/Shihezi University School of Medicine, Shihezi, Xinjiang, China.
  • 2 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital/Shihezi University School of Medicine, Shihezi, Xinjiang, China; Department of Clinical Laboratory, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 3 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital/Shihezi University School of Medicine, Shihezi, Xinjiang, China; Department of Pathology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 4 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital/Shihezi University School of Medicine, Shihezi, Xinjiang, China. Electronic address: houjun229@163.com.
  • 5 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital/Shihezi University School of Medicine, Shihezi, Xinjiang, China. Electronic address: lh_wang@shzu.edu.cn.
PMID: 39549546 DOI: 10.1016/j.intimp.2024.113591
Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Chemotherapy using cisplatin, a drug that damages deoxyribonucleic acid (DNA), is not very effective in treating HCC due to its side effects and drug resistance. Manganese (Mn2+), a trace element, has been shown to enhance immune responses, but its ability to improve cisplatin-induced antitumor immunity in HCC remains unclear. The present study found that treatment with Mn2+ in combination with cisplatin promoted Cyclic GMP-AMP Synthase (cGAS)-stimulator of interferon genes (STING) signaling activation and C-X-C motif chemokine ligand 10 (CXCL10) production in tumor and dendritic cells. CXCL10 is associated with CD8a levels, and its high expression is linked to better prognosis in patients with HCC. In addition, Mn2+ and cisplatin co-treatment enhanced the recruitment of CD8+ T cells through the CXCL10/CXCR3 axis. Similarly, in an orthotopic transplantation tumor model, STING activation, CD8+ T cell infiltration, and tumor cell killing levels were higher in the combined treatment group. The above findings suggest that utilizing Mn2+ in combination with cisplatin could be a potential treatment option for HCC.

Keywords

CD8(+) T cells; CXCL10; Cisplatin; HCC; Mn(2+); cGAS-STING.

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