Nikhil Joshi, Ph.D.

Nikhil Joshi, Ph.D.

Institution: Yale University School of Medicine

Project: Investigating the function of tumor-specific T cells in non-small cell lung

Grant(s): Lung Cancer Discovery Award

Therapies targeting immune cells have revolutionized the treatment of lung cancer. These therapies work by driving immune cells called T cells to killing cancer cells, which leads to the elimination of the disease. Yet, immune-targeting therapies do not work in most patients. To understand why, scientists have been looking at T cells inside cancers from patients, trying to figure out how to fix them. Our research has shown that another source of T cells comes from the tumor draining lymph node, and that the T cells in the lymph node may be better targets for immune-targeting therapies. We will identify if lymph node T cells are present in lung cancer patients and tests drugs that could be used to improve immune targeting therapies in lung cancer patients.

Update:

Using models of lung adenocarcinoma, we identified that animals with developing lung tumors have tumor-draining lymph node glands that contain anti-tumor T cells, and that these T cells form a highly functional and stable reservoir. These lymph node T cells are maintained in animals even in “cold” tumors, which mirror patients that do not respond to immunotherapy. T cells naturally travel from the lymph node to the tumor at a low rate, which is how our body slows the growth of cancer, and we believe this travel is important for the success of immunotherapy. We are currently developing therapies to drive T cells into tumors, which we believe will be the key to helping non-responsive patients.

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