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Updated: Jun 13, 2025

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TUMOR-INFILTRATING NOCICEPTOR NEURONS PROMOTE IMMUNOSUPPRESSION

Anthony C Restaino1, Maryam Ahmadi2, Amin Reza Nikpoor2

  • 1Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, USA.

Biorxiv : the Preprint Server for Biology
|September 10, 2024
PubMed

Insights

Nociceptor neurons, or pain-sensing nerves, promote tumor growth by increasing immunosuppressive cells. Blocking IL-6 released by these nerves may enhance anti-cancer immunity.

Area of Science:

  • Neuroscience
  • Immunology
  • Oncology

Background:

  • Nociceptor neurons, traditionally linked to pain, play an underappreciated role in cancer immunity.
  • Tumor-associated inflammation and immune suppression are critical barriers to effective cancer therapy.

Purpose of the Study:

  • To investigate the impact of nociceptor neurons on tumor immunity and identify potential therapeutic targets.
  • To elucidate the mechanisms by which cancer cells interact with nociceptor neurons.

Main Methods:

  • Mouse models of head and neck carcinoma and melanoma.
  • Analysis of myeloid-derived suppressor cell (MDSC) infiltration.
  • Culture of dorsal root ganglia (DRG) neurons with cancer-derived small extracellular vesicles (sEVs).
  • Assessment of T-cell exhaustion markers and cytokine profiles.

Main Results:

  • Removal of nociceptor neurons reduced MDSC infiltration and tumor growth in mouse models.
  • Cancer sEVs attracted nociceptive nerves to tumors and increased neuronal expression of Substance P and IL-6.
  • Exposure to cancer sEVs and CD8+ T-cells induced an immunosuppressive state, increasing T-cell exhaustion.
  • Cancer patient sEVs increased nociceptor sensitivity.

Conclusions:

  • Nociceptor neurons facilitate tumor immune evasion by promoting MDSC infiltration and CD8+ T-cell exhaustion.
  • Targeting IL-6 released by nociceptor neurons is a potential strategy to enhance anti-tumor immunity.

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