2. Academic Validation
  3. Mitochondrial transfer from immune to tumor cells enables lymph node metastasis

Mitochondrial transfer from immune to tumor cells enables lymph node metastasis

  • Cell Metab. 2026 Feb 3;38(2):388-398.e7. doi: 10.1016/j.cmet.2025.12.014.
Azusa Terasaki 1,  Keshav Bhatnagar 1,  Alexis T Weiner 1,  Yuhao Tan 2,  Viktoria Szeifert 1,  Han-Li Huang 1,  Lukas Wiggers 1,  Viviana Rodrigues 1,  Cara C Rada 3,  Vishnu Shankar 4,  Suguru Saito 5,  Peter Ofori Ankomah 6,  Theodore Roth 7,  Bill Chiu 8,  Robert West 1,  Lingyin Li 9,  Nathan Reticker-Flynn 10,  Jeffrey D Axelrod 1,  Jonathan R Brestoff 11,  Bo Li 2,  Edgar Engleman 12,  Derick Okwan-Duodu 13
Affiliations

Affiliations

  • 1 Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • 2 Children's Hospital of Pennsylvania, Philadelphia, PA, USA.
  • 3 Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • 4 Immunology Graduate Program, Stanford University, Stanford, CA 94305, USA.
  • 5 Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90066, USA.
  • 6 Massachusetts General Hospital, Boston, MA, USA.
  • 7 Department of Pathology, Stanford University, Stanford, CA 94305, USA; Arc Institute, Palo Alto, CA, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • 8 Department of Surgery, Stanford University, Stanford, CA 94305, USA.
  • 9 Arc Institute, Palo Alto, CA, USA; Department of Biochemistry, Program in Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.
  • 10 Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Otolaryngology, Stanford University, Stanford, CA 94305, USA.
  • 11 Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
  • 12 Department of Pathology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
  • 13 Department of Pathology, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA. Electronic address: [email protected].
PMID: 41529696 DOI: 10.1016/j.cmet.2025.12.014
Abstract

Although the immune system is a significant barrier to tumor growth and spread, established tumors evade immune attack and frequently colonize immune populated areas such as the lymph node. The mechanisms by which Cancer cells subvert the tumor-immune microenvironment to favor spread to the lymph node remain incompletely understood. Here, we show that, as a common attribute, tumor cells hijack mitochondria from a wide array of immune cells. Mitochondria loss by immune cells decreases antigen-presentation and co-stimulatory machinery, as well as reducing the activation and cytotoxic capacity of natural killer (NK) and CD8 T cells. In Cancer cells, the exogenous mitochondria fuse with endogenous mitochondria networks, leak mtDNA into the cytosol, and stimulate cGAS/STING, activating type I interferon-mediated immune evasion programs. Blocking mitochondrial transfer machinery-including cGAS, STING, or type I interferon-reduced Cancer metastasis to the lymph node. These findings suggest that Cancer cells leverage mitochondria hijacking to weaken anti-tumor immunosurveillance and use the acquired mitochondria to fuel the immunological requirements of lymph node colonization.

Keywords

MERCI; cGAS/STING; immune evasion; lymph node cancer metastasis; mitochondrial transfer.

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