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  • Poster presentation
  • Open Access

Modulation of anti-tumor lymphocyte function by neurotransmitter glutamate

  • 1,
  • 1 and
  • 2
Journal for ImmunoTherapy of Cancer20142 (Suppl 3) :P38

https://doi.org/10.1186/2051-1426-2-S3-P38

  • Published:

Keywords

  • Multiple Sclerosis
  • Glutamate
  • Glutamate Receptor
  • Receptor AMPA
  • Neurotransmitter Glutamate

Most research to date pertaining to neural influence on immune response involves immunosuppression via the anti-inflammatory pathway. However, there is emerging evidence indicating that neurotransmitters have the ability to promote immune activation. We are investigating whether neurotransmitters can modulate and/or activate T cell function in situations where immunosuppression is prevalent such as in the tumor microenvironment. Published work suggests that glutamate, serotonin, dopamine, and Substance P trigger immune responses such as cytokine secretion, integrin expression, and chemotaxis. We saw that both CD4 and CD8 T cells express high surface protein levels of glutamate receptor AMPA iGluR3, which is able to import Ca2+ and Na+. We also found that mGluR1 is significantly upregulated on lymphocytes upon activation. Our data further show that T cells in the tumor-draining LN and tumor-infiltrating lymphocytes have upregulated expression of iGluR3 and mGluR1. Treatment with glutamate or its receptor agonist augmented T cell proliferation following CD3-CD28-mediated TCR stimulation. Thus, modulation of glutamate receptor signaling can be useful for enhancing anti-tumor T cell immunity such as inhibition of AICD, enhancement of proliferation, and increased cytokine production [1, 2]. Indeed, overactivation of lymphocytes in multiple sclerosis is closely tied to the overexpression of AMPA GluR3 on T cells [3]. Experiments are under way to dissect in an adoptive transfer set up whether glutamate-modulated immune effector function involves specific activation of anti-tumor lymphocytes to elicit cytolytic response that is needed to cause tumor cell death. Our findings will help identify novel neuro-immune modulators that may serve to enhance anti-tumor T cell response.

Authors’ Affiliations

(1)
Meharry Medical College School of Medicine, Nashville, TN, United States
(2)
Meharry Medical College School of Medicine / Vanderbilt-Ingram Cancer Center, Nashville, TN, United States

References

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  2. Pacheco R, Oliva H, Martinez-Navio JM, Climent N, Ciruela F, Gatell JM, Gallart T, Mallol J, Lluis C, Franco R: Glutamate released by dendritic cells as a novel modulator of T cell activation. J Immunol. 2006, 177: 6695-6704. 10.4049/jimmunol.177.10.6695.View ArticlePubMedGoogle Scholar
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