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Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer.

Authors
  • Ganesan, Anusha-Preethi1, 2
  • Clarke, James1, 3
  • Wood, Oliver3
  • Garrido-Martin, Eva M4
  • Chee, Serena J3, 5
  • Mellows, Toby4
  • Samaniego-Castruita, Daniela1
  • Singh, Divya1
  • Seumois, Grégory1
  • Alzetani, Aiman5
  • Woo, Edwin5
  • Friedmann, Peter S4
  • King, Emma V3
  • Thomas, Gareth J3
  • Sanchez-Elsner, Tilman4
  • Vijayanand, Pandurangan1, 4
  • Ottensmeier, Christian H3, 5
  • 1 La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
  • 2 Division of Pediatric Hematology Oncology, Rady Children's Hospital, University of California San Diego, San Diego, California, USA.
  • 3 Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • 4 Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine University of Southampton, Southampton, UK.
  • 5 Southampton University Hospitals NHS foundation Trust, Southampton, UK.
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Publication Date
Aug 01, 2017
Volume
18
Issue
8
Pages
940–950
Identifiers
DOI: 10.1038/ni.3775
PMID: 28628092
Source
Medline
License
Unknown

Abstract

Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3. Tumors with a high density of CTLs showed enrichment for transcripts linked to tissue-resident memory cells (TRM cells), such as CD103, and CTLs from CD103hi tumors displayed features of enhanced cytotoxicity. A greater density of TRM cells in tumors was predictive of a better survival outcome in lung cancer, and this effect was independent of that conferred by CTL density. Here we define the 'molecular fingerprint' of tumor-infiltrating CTLs and identify potentially new targets for immunotherapy.

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