Transcriptome profiling of purified CD8+ TILs from treatment-naive lung or head and neck cancer patients revealed commonalities in the expression of genes associated with exhaustion and activation, suggestive of continued stimulation, and novel heterogeneity in the expression of CD103, a marker of resident memory cells, which is linked to survival outcomes in lung cancer.
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.
Author Info: (1) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. Division of Pediatric Hematology Oncology, Rady Children's Hospital, University of California San Diego,
Author Info: (1) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. Division of Pediatric Hematology Oncology, Rady Children's Hospital, University of California San Diego, San Diego, California, USA. (2) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK. (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) Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK. Southampton University Hospitals NHS foundation Trust, Southampton, UK. (6) Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine University of Southampton, Southampton, UK. (7) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. (8) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. (9) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. (10) Southampton University Hospitals NHS foundation Trust, Southampton, UK. (11) Southampton University Hospitals NHS foundation Trust, Southampton, UK. (12) Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine University of Southampton, Southampton, UK. (13) Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK. (14) Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK. (15) Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine University of Southampton, Southampton, UK. (16) La Jolla Institute for Allergy &Immunology, La Jolla, California, USA. Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine University of Southampton, Southampton, UK. (17) Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK. Southampton University Hospitals NHS foundation Trust, Southampton, UK.
