CTSI Distinguished Seminars feature important topics in clinical and translational science presented by outstanding, and sometimes world-renowned, speakers.
Through the Seminar Series, UB's Clinical and Translational Science Institute is partnering with the five health sciences schools and Roswell Park Comprehensive Cancer Center to sponsor a round of visiting scholars in the forefront of their respective disciplines. The goal is to expose faculty, trainees and students to various pathways in clinical and translational research.
Distinguished Professor and Vice Chair
Department of Immunology
Leader, Cancer Immunology Program
Co-Director, Tumor Microenvironment Center
Scientific Director, Fondazione Ri.MED
School of Medicine
University of Pittsburgh
Immunotherapies targeting the PD1/PDL1 pathway have had a major impact on cancer treatment. However, only a proportion of patients respond, and an even smaller proportion exhibit a long-term, durable cure. Several mechanisms of resistance and potential combinatorial approaches will be discussed. Lack of response to inhibitory receptor (IR) blockade therapy and increased disease burden has been associated with circulating, peripheral CD8+ T cell exhaustion, which is defined by poor T cell function linked to increased IR expression (eg: PD1, LAG3, neuropilin-1 [NRP1]). LAG3 is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. However, persistent antigen exposure in the tumor microenvironment results in sustained PD1/LAG3 expression, contributing to a state of exhaustion manifest in impaired proliferation and cytokine production. Lastly, regulatory T cells (Tregs) inhibit beneficial anti-tumor responses. Treg depletion enhances tumor rejection in animal models and the clinic but also leads to substantial adverse events. Thus, approaches have been sought to target Tregs in tumors while limiting systemic autoimmune and inflammatory manifestations. Thinking more holistically on the tumor microbome and understanding the various cell types, molecules and mechanisms will enhance future treatments for all patients with cancer.