Targeting Cytotoxic T-Lymphocyte Antigen 4 in Immunotherapies for Melanoma and Other Cancers

Abstract

The immune system can simultaneously protect against tumor growth and sculpt resistant tumor strains. By a variety of mechanisms, anti-cytotoxic T-lymphocyte antigen (CTLA)-4 therapy may shift such opposing forces towards tumor elimination. In recent clinical trials, anti-CTLA-4 therapy induces durable responses that correlate with markers of immune activity, such as antigen-specific CD4⁺ or CD8⁺ cytokine release, antitumor antibody formation or cellular phenotype differentiation. However, some patients exhibit atypical responses to anti-CTLA-4 therapy, demonstrating transient/delayed responses or heterogeneity by lesion site. Such atypical responses may offer insight into the mechanism of anti-CTLA-4 therapy. The immunogram – a newly described graphical synthesis of treatment data and immune correlates in individual patients – may help us to confirm, reject or formulate new hypotheses regarding the mechanism of anti-CTLA-4 activity.

KEYWORDS::

• cytotoxic T-lymphocyte antigen 4 blockade
• immune surveillance
• immunoediting
• immunogram
• immunotherapy
• ipilimumab
• melanoma
• tremelimumab

Acknowledgements

We thank Dr Lloyd J Old for providing scientific guidance in developing the immunogram.

Financial & competing interests discolure

Jedd D Wolchok is a consultant to Bristol-Myers Squibb and Medarex. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.