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Tissue-resident memory T cells play an important role in protecting against pathogens by responding rapidly and recruiting key immune cell populations. We have found that tissue-resident memory T cells respond early during cancer immunotherapy in patients treated with immune checkpoint blockade. These cells proliferate extensively during therapy and have a cytotoxic program. Tissue-resident memory T cells also play an important role in immune-related adverse events of immunotherapy.
Kai Wucherpfennig is chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and is the co-leader of the Cancer Immunology Program of the Dana-Farber/Harvard Cancer Center. He has made important contributions to immunology, in particular on the study of T cells which are key effector cells of protective tumor immunity. His work led to the discovery of mechanisms of resistance to cancer immunotherapy which his lab is using to develop next-generation cancer immunotherapies.
The Wucherpfenning Lab focuses on the molecular mechanisms that control the activity of T cells and NK cells in cancer immunity. His lab integrates study of the human immune system in the context of cancer immunotherapy with investigation of discovered pathways in relevant model systems. The lab recently discovered that tissue-resident memory T cells are early responders to immune checkpoint blockade in HNSCC patients (Cell 2022), indicating that a tissue-residency program is a critical element of protective tumor immunity. Reactivation of tissue-resident memory T cells is also an important cause of immune-related adverse events, as shown in melanoma patients who developed colitis during immune checkpoint blockade therapy (Cell 2021). The PI’s lab has also discovered novel resistance mechanisms by investigation of human cancers. For example, his lab recently showed that the inhibitory CD161 receptor is highly induced on T cells in human gliomas and other cancers (Cell 2021).