2. Academic Validation
  3. Inhibiting SLAMF8 modulates tumor-associated macrophages and restores CD8+ T cell-mediated antitumor immunity in colorectal cancer

Inhibiting SLAMF8 modulates tumor-associated macrophages and restores CD8+ T cell-mediated antitumor immunity in colorectal cancer

  • Oncoimmunology. 2025 Dec 31;14(1):2581910. doi: 10.1080/2162402X.2025.2581910.
Xingzhi Han 1 2,  Xueying Bai 2 3,  Ning Wang 2 3,  Yuexin Sun 2 4,  Jing Hu 2,  Li Li 2,  Zhihao Liu 5,  Yaping Zhang 6,  Zixin Liang 4,  Liuqi Sang 7,  Lu Han 4,  Qun Zhang 2,  Xiaoping Qian 1 2
Affiliations

Affiliations

  • 1 Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.
  • 2 Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
  • 3 Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PPeople's Republic of China.
  • 4 Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.
  • 5 Minhang Hospital, Fudan University, Shanghai, People's Republic of China.
  • 6 Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China.
  • 7 Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, People's Republic of China.
PMID: 41211891 DOI: 10.1080/2162402X.2025.2581910
Abstract

SLAMF8 is predominantly expressed in macrophages and plays an important role in autoimmune diseases and inflammation. Our previous studies have focused on SLAMF8, however, the potential of SLAMF8 as an immunotherapeutic target and its role in regulating the tumor immune microenvironment remain to be elucidated. This study demonstrated that macrophage-specific SLAMF8 is significantly associated with a poor prognosis for colorectal Cancer (CRC). Additionally, M2 macrophage and tumor-associated macrophages (TAMs) models were used to verify that SLAMF8 induces an immunosuppressive phenotype in macrophages and regulates antitumor immunity by inhibiting the activation and function of CD8+ T cells. In vivo, we confirmed that SLAMF8 inhibition promoted remodeling of the immunosuppressive microenvironment and augmented immunotherapy sensitivity in CRC. Mechanistically, we demonstrated that SLAMF8 promotes the polarization of macrophages toward the M2 phenotype via the PI3K/Akt and JAK/STAT3 signaling pathways. In summary, this study confirmed that inhibiting SLAMF8 exerts an antitumor effect by reversing the immunosuppressive tumor microenvironment in CRC, providing new therapeutic targets and strategies for combined immunotherapy.

Keywords

Colorectal cancer; SLAMF8; immunotherapy; tumor microenvironment; tumor-associated macrophage.

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