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Modulation of anti-tumor lymphocyte function by neurotransmitter glutamate
  1. Thomas Hodo1,
  2. Menaka Thounaojam1 and
  3. Anil Shanker2
  1. Aff1 grid.259870.1000000010286752XMeharry Medical College School of Medicine Nashville TN United States
  2. Aff2 grid.259870.1000000010286752XMeharry Medical College School of Medicine / Vanderbilt-Ingram Cancer Center Nashville TN United States

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Meeting abstracts

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.


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