Encouraging Intolerance

Blocking CTLA4 can disrupt the development of tolerance and enhance the body’s antitumor efforts, but we have not yet found the right agents.

Cytotoxic T lymphocyte–associated antigen 4 (CTLA4) is an inhibitory receptor whose activity results in downregulated T-cell activation and impaired cellular immune functions. CTLA4 is part of the crucial immunological network that leads to tolerance. In the normal context, tolerance is critical in preventing unwanted autoimmune disease; however, in the case of metastatic melanoma, tolerance to the tumor leads to failed immunosurveillance. In two phase I/II studies, researchers recently examined the clinical impact on metastatic melanoma of CTLA4 blockade with the anti-CTLA4 antibodies ipilimumab and tremelimumab.

In the first study, 88 patients with metastatic melanoma received ipilimumab at various dosing schedules. In all, 4 patients had …

Reviewing Author

Hensin Tsao, MD, PhD

Disclosures

Consultant / advisory board Lubax; WorldCare Clinical

EquityLubax

Grant / Research support NIH; Department of Defense; American Skin Association; Piramal

Editorial boardsBritish Journal of Dermatology; Journal of the American Academy of Dermatology; Journal of Investigative Dermatology

Leadership positions in professional societies American Academy of Dermatology (Chair, Skin Cancer and Melanoma Committee); American Board of Dermatology (Director)