2. Academic Validation
  3. Antigen Cross-Presentation by Type-2 Innate Lymphoid Cells Facilitates the Activation of Antitumor CD8+ T Cells

Antigen Cross-Presentation by Type-2 Innate Lymphoid Cells Facilitates the Activation of Antitumor CD8+ T Cells

  • Cancer Res. 2025 Jul 15;85(14):2659-2678. doi: 10.1158/0008-5472.CAN-24-4194.
Jihyun Kim 1 2,  Seung Geun Song 3 4,  Suhyun Park 1 5,  Young Gyun Ko 1 5,  Jongho Ham 1 5,  TaeSoo Kim 6,  Sang-Jun Ha 7 8,  Yong-Soo Bae 8 9,  Doo Hyun Chung 3 4,  Hye Young Kim 1 2 5 6 8
Affiliations

Affiliations

  • 1 Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
  • 2 Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
  • 3 Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 4 Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
  • 5 Department of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, Korea.
  • 6 Department of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul, Korea.
  • 7 System Immunology Laboratory, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
  • 8 SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon, Korea.
  • 9 Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
PMID: 40245114 DOI: 10.1158/0008-5472.CAN-24-4194
Abstract

Type-2 innate lymphoid cells (ILC2) exhibit dual functions in Cancer, both promoting and inhibiting tumor growth by regulating antitumor immune responses. Elucidation of the precise mechanisms by which ILCs regulate adaptive immune responses could support the development of improved immunotherapeutic approaches. In this study, we revealed that ILC2s possess the capacity to internalize, process, and present exogenous tumor antigen on MHC-I molecules, along with costimulatory molecules, to CD8+ T cells, thereby inducing their differentiation into CTLs. Transferring ILC2s into tumor-bearing mice resulted in CD8+ T-cell-dependent inhibition of tumor growth. Moreover, coculturing CD8+ T cells with ILC2s upregulated the expression of cytotoxic molecules, leading to efficient killing of Cancer cells in vitro as well as in vivo upon transfer into tumor-bearing mice. Mechanistically, ILC2s employed clathrin-dependent endocytosis to internalize exogenous antigens and process/present them to CD8+ T cells as effectively as conventional antigen-presenting cells. Based on this study, ILC2s emerge as proficient antigen-presenting cells capable of stimulating the tumor-killing activity of CD8+ T cells, thus offering promising antitumor immunotherapeutic strategies.

Significance: Type-2 innate lymphoid cells process and present tumor antigens to CD8+ T cells to increase cytotoxic activity against Cancer cells, highlighting the potential to harness this intercellular interaction to improve Cancer treatment.

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