AI Summary
The two studies published in Cell by University of Pittsburgh researchers reveal how immunotherapies targeting the immune checkpoints PD1 and LAG3 work together to activate immune responses in melanoma. The findings demonstrate why combining therapies that target both checkpoints can be more effective for patients compared to therapies targeting only PD1. These studies provide important insights into the mechanisms underlying the effectiveness of combination therapies and shed light on how drugs can be optimized for better treatment outcomes in cancer patients.
Two studies published in the latest issue of the journal Cell by University of Pittsburgh researchers uncover how immunotherapies targeting the immune checkpoints PD1 and LAG3 work together to activate immune responses. The findings shed light on why combination therapies targeting both checkpoints can improve outcomes for melanoma patients compared to monotherapies targeting only PD1.
Using data from a human clinical trial and animal models, the researchers investigated responses of tumor-killing CD8+ T cells. During extended battles with cancer, immune checkpoints accumulate on the surface of T cells, acting like brakes on their activity and driving exhaustion. Immune checkpoint inhibitors that help release these brakes and combat T cell exhaustion have revolutionized cancer treatment, but because many patients don’t respond, more research is needed to understand how these drugs can be combined to improve their effectiveness.
These studies are the first in-depth interrogation of the immune system’s response to blocking PD1 and LAG3. We found that targeting PD1 versus both PD1 and LAG3 modulated the function of CD8+ T cells in surprisingly different ways. Understanding these mechanisms is relevant for how we think about combination therapies and optimizing which drugs pair best.”
Dario A. A. Vignali, Ph.D., chair and distinguished professor of the Department of Immunology at Pitt, senior author on two of the papers
In 2022, the LAG3-targeting drug relatlimab was approved by the U.S. Food and Drug Administration as a combination treatment with nivolumab, which targets PD1, for patients with metastatic melanoma. This combination has been shown