Description:

Title: LAG-3: The Third Checkpoint Inhibitor & its Synergistic Interactions with PD1

Speaker: Dario A. A. Vignali, PhD,

Chair and Distinguished Professor

The Frank Dixon Chair in Cancer Immunology

Co-Director, Cancer Immunology Training Program

Department of Immunology

University of Pittsburgh School of Medicine

Topic:

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. This presentation will include a brief introduction LAG3, discussion of the signaling mechanism used by LAG3, and assessment of new insight into the function of LAG3, alone and in combination with PD1, from mouse models of cancer and analysis of samples from patients treated with LAG3/PD1 therapeutics.

Host: Joseph Podojil, PhD, Dept. of Microbiology-Immunology