Giovanni Galletti, PhD, Postdoctoral Fellow University of California, San Diego The immune system is our best line of defense against malignancy. Specialized immune cells, termed T cells, patrol our body ready to fight against infections and cancer. T cells can be overwhelmed by the tumor’s influence, progressively losing their capacity to kill malignant cells and become ‘exhausted’. Tumors can produce specific proteins that exploit ‘immune checkpoints’ to promote this state of T cell exhaustion to avoid detection by the T cells and continue to spread. However, the introduction of immune checkpoint therapy that blocks these proteins can effectively reinvigorate exhausted T cells and help them fight the cancer. Additionally, a new T cell-type, called tissue-resident memory T cells, appears particularly well-suited to adapt to tissues and possesses specific, yet unknown, properties that make them highly effective at suppressing tumor growth. Dr. Galletti is particularly intrigued by the capacity of these cells to present traits simultaneously associated with exhausted and non-exhausted cells, especially at barrier tissues such as the gut. Thus, Dr. Galletti hypothesizes that we can learn from the way these T cells work in these sites under healthy and pathological conditions, also in the context of immune checkpoint therapy, to better understand the factors regulating their properties to prevail in their battle against cancer. These studies will shed light on why our immune system is unable to suppress cancer while uncovering novel strategies to reinvigorate the exhausted immune response. The insights obtained by this research will have broad applications to improve the standard of care for most solid tumors. Projects and Grants Programming exhaustion resistance in T lymphocytes for cancer immunotherapy University of California, San Diego | All Cancers | 2022 | Ananda Goldrath, Ph.D.