articleScience Translational MedicineMar 1, 2017GREEN OA

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

WRWhijae RohPCPei-Ling ChenARAlexandre ReubenCNChristine N. SpencerPAPeter A. Prieto

The University of Texas MD Anderson Cancer Center · AC Camargo Hospital · +3 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Immune checkpoint blockade produces clinical benefit in many patients. However, better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T cell receptor sequencing and whole-exome sequencing within the same cohort and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4…

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Topics & keywords

Topics
Keywords
  • Blockade
  • Immune checkpoint
  • CTLA-4
  • Immune system
  • Melanoma
  • Exome sequencing
  • Cytotoxic T cell
  • Immunotherapy
UN Sustainable Development Goals
  • Good health and well-being
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