A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade

Research output: Contribution to journalArticle

Authors

  • Daniela S. Thommen
  • Viktor H. Koelzer
  • Petra Herzig
  • Andreas Roller
  • Marcel Trefny
  • Anna Kiialainen
  • Jonathan Hanhart
  • Catherine Schill
  • Christoph Hess
  • Spasenija Savic Prince
  • Mark Wiese
  • Didier Lardinois
  • Ping-Chih Ho
  • Christian Klein
  • Vaios Karanikas
  • Kirsten D. Mertz
  • Ton N. Schumacher
  • Alfred Zippelius

Abstract

Evidence from mouse chronic viral infection models suggests that CD8+ T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1-) from non-small-cell lung cancer patients. PD-1T T cells showed a markedly different transcriptional and metabolic profile from PD-1N and PD-1- lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention.

Details

Original languageEnglish
JournalNature Medicine
Publication statusPublished - 11 Jun 2018

Keywords

  • Cancer microenvironment, Non-small-cell lung cancer, Tumour immunology