ATF3+ tumor-innervating neurons control anti-cancer immunity
Itch is a common feature of various cancers, while cancer cells actively secrete factors promoting neuronal infiltration of tumors. Experimentally stopping the electrical signals of tumor infiltrating neurons helps decrease tumor growth, but the specific means by which neurons regulate cancer cells survival is yet to be uncovered. Given that we discovered that cancer cells drive major changes in the gene expression profiles of tumor-infiltrating noxious detecting neurons, we hypothesize that cancer cells exploit nociceptors interplay with the immune system to sustain their growth and survival. To investigate this, we aim to study: 1) whether cancer cells directly activate these nociceptors, 2) nociceptor-induced expression of immune checkpoint receptors on NK cells, and 3) the role of nociceptors in cancer immunosurveillance. Studying the biology of cancer, by simultaneously embracing the disease’s nervous and immune aspects, as well as their reciprocal interplay, will likely lead to the discovery of unexpected biology and novel therapeutic avenues. As such, this proposal represents the first attempt to amplify the immune system’s capacity to fight cancer cells by harnessing the nervous and immune system’s interplay.