Emergence of High-Avidity Melan-A-Specific Clonotypes as a Reflection of Anti-PD-1 Clinical Efficacy

Cancer Res. 2017 Dec 15;77(24):7083-7093. doi: 10.1158/0008-5472.CAN-17-1856. Epub 2017 Dec 6.


Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A-specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti-PD-1. We observed amplification of Melan-A-specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response. These emerging Vß subfamilies displayed a higher functional avidity for their cognate antigen than Vß subfamilies not amplified upon anti-PD-1 therapy and could be identified by a sustained coexpression of PD-1 and TIGIT receptors. Thus, in addition to the emergence of neoantigen-specific T cells previously documented upon anti-PD-1 therapy, our work describes the emergence of high-avidity Melan-A-specific clonotypes as a surrogate marker of treatment efficacy. Cancer Res; 77(24); 7083-93. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibody Affinity*
  • Antibody Formation
  • Antigens, Neoplasm / immunology
  • Cells, Cultured
  • Clone Cells
  • Humans
  • Immunotherapy / methods*
  • MART-1 Antigen / immunology*
  • MART-1 Antigen / metabolism
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Programmed Cell Death 1 Receptor / immunology*
  • Substrate Specificity
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • MART-1 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor