Linyu Sun, PhD, Postdoctoral Fellow Brigham & Women's Hospital/Harvard Medical School Area of Research: Leukemia Checkpoint blockade immunotherapy has achieved durable responses in several solid tumor types by reinvigorating the anti-tumor function of T cells. However, many patients have shown limited responses and successful checkpoint blockade in solid tumors has exhibited little benefit in blood cancers, highlighting the significant importance of uncovering the unknown alternative immune-suppressive mechanism in hematologic malignancies. TIM-3 was originally identified as an inhibitory checkpoint receptor expressed on IFNγ-producing T cells in Dr. Kuchroo’s lab. More recently, they have reported that TIM-3 is also expressed on dendritic cells (DCs), where it regulates inflammasome activation and tumor growth. Moreover, TIM-3 has been observed to specifically express on leukemic stem cells in blood cancers, especially myeloid-lineage leukemia. Importantly, anti-Tim-3 antibody (MBG453, Sabatolimab) blockade has shown promising response rates in acute myeloid leukemia/myelodysplastic syndrome patients. As the dysfunction of immune checkpoint regulation is a major impediment to effective cancer immunotherapy, investigating the mechanism of these inhibitory checkpoint receptors in blood cancers is critical for the development of successful immune-based therapies. Targeting the unexplored TIM-3-driven pathways in myeloid cells may not only have the potential to inhibit the intrinsic unlimited proliferation of leukemic cells, but may also boost the extrinsic anti-tumor immune response, emphasizing a “one stone kills two birds” effect. Furthermore, mechanistically characterizing the immune-regulating role of TIM-3 in leukemia will provide long-missing information for understanding the use of checkpoint inhibitors in treating liquid tumors. Overall, Dr. Sun’s work may facilitate the development of new cancer therapeutic regimens. Projects and Grants Role of TIM-3 in regulating anti-tumor immunity in AML Brigham & Women’s Hospital/Harvard Medical School | Leukemia | 2023 | Vijay Kumar Kuchroo, PhD
