Dr. Talbot studies the dialogue between the nervous and immune systems. It is well demonstrated that pain and itch are common features of various cancers, and that cancer cells actively secrete factors promoting neuronal infiltration of tumors. Recent data suggests that 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.
We recently discovered that cancer cells drive major changes in the gene expression profiles of tumor-infiltrating noxious-detecting neurons. To assess how the dialogue between cancer cells and sensory neurons impact immune surveillance functioning, we aim to define 1) which mediators produced by nociceptor neurons controls the exhaustion of immune cells. Finally, given that chemotherapeutic agents directly activate sensory neurons leading to painful manifestation, we aim to study 2) whether chemotherapeutics, by acting on sensory neurons, may lead to immune exhaustion.
Studying the biology of cancer with a holistic approach, 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. Altogether, the local silencing of nociceptor-innervating tumors specifically targeted to boost immune function, represents a groundbreaking complement to chemotherapy and immune checkpoint inhibitors.