Skip to main content
  • Keynote speaker presentation
  • Open access
  • Published:

Targeting multiple inhibitory receptors to reverse melanoma-induced T cell dysfunction

It is now clearly established that dysfunctional/exhausted TA-specific T cells present in peripheral blood and at tumor sites co-express multiple inhibitory receptors. The implications of this important finding are two-fold. First, multiple subsets of TA-specific T cells can be identified in patients with advanced melanoma that exhibit variable levels of T cell dysfunction. Second, this observation supports the implementation of combinatorial therapies aiming at blocking multiple inhibitory pathways to enhance TA-specific immune responses and reverse tumor-induced T cell dysfunction. We have shown that a subset of highly dysfunctional TA-specific CD8+ T cells isolated from patients with advanced melanoma upregulate both PD-1 and Tim-3. PD-1 and Tim-3 blockades strongly enhance TA-specific CD8+ T cell expansion and function. Accordingly, targeting PD-1 and Tim-3 in vivo induces melanoma regression in mice. Therefore, the combination of PD-1 and Tim-3 blockade either alone or in combination with cancer vaccines appears to be a promising potent approach to reverse melanoma-induced T cell dysfunction and promote tumor regression in patients with advanced melanoma.

Author information

Authors and Affiliations


Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zarour, H.M. Targeting multiple inhibitory receptors to reverse melanoma-induced T cell dysfunction. J Transl Med 13 (Suppl 1), K14 (2015).

Download citation

  • Published:

  • DOI: