Corgnac et al. analyzed a group of 111 patients with advanced NSCLC previously treated with anti-PD-L1. Responding patients whose pre-therapy tumors were heavily infiltrated by CD103+CD8+ resident memory (CD103+ TRM) T cells had dramatically increased progression-free survival (median 30 months) compared to patients with low numbers (median 2.3 months). Unlike in non-responders, CD103+ TRM cells increased in responding patients’ tumors after treatment with anti-PD-L1, were enriched with tumor Ag-specific cells expressing oligoclonal TCR clonotypes, and contained a subset expressing IL-17 and IFNγ, suggestive of Th17/Tc17 cells.
Contributed by Katherine Turner
ABSTRACT: Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103+CD8+ lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes. The density of CD103+CD8+ cells increases during immunotherapy in most responder, but not in non-responder, patients. CD103+CD8+ cells co-express CD49a and CD69 and display a molecular profile characterized by the expression of PD-1 and CD39. CD103+CD8+ tumor TRM, but not CD103−CD8+ tumor-infiltrating counterparts, express Aiolos, phosphorylated STAT-3, and IL-17; demonstrate enhanced proliferation and cytotoxicity toward autologous cancer cells; and frequently display oligoclonal expansion of TCR-β clonotypes. These results explain why CD103+CD8+ TRM are associated with better outcomes in anti-PD-(L)1-treated patients.
Author Info: (1) INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculte de Medecine, Universite Paris-Sud, Universite Paris-Saclay, 94805 Villejuif, France (2)
Author Info: (1) INSERM UMR 1186, Integrative Tumor Immunology and Immunotherapy, Gustave Roussy, Faculte de Medecine, Universite Paris-Sud, Universite Paris-Saclay, 94805 Villejuif, France (2) Department of Cancer Medicine, Gustave Roussy, Institut d’Oncologie Thoracique, Gustave Roussy, Universite Paris-Saclay, 94805 Villejuif, France (3) Gastrointestinal and Medical Oncology Department, Hopital Europeen Georges Pompidou, Paris, France (4) INSERM Unit U981, Department of Experimental Pathology, Gustave Roussy, Universite Paris-Sud, Universite Paris-Saclay, 94805 Villejuif, France (5) Department of Biology and Medical Pathology, Gustave Roussy, 94805 Villejuif, France (6) Hopital Marie-Lannelongue, Service d’Anatomie Pathologique, 92350 Le-Plessis-Robinson, France (7) Institut Mutualiste Montsouris, Service d’Anatomie Pathologique, 75014 Paris, France (8) Drug Development Department, Gustave Roussy, Universite Paris-Saclay, 94805 Villejuif, France (9) These authors contributed equally (10) Present address: Laboratory of Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), and Medical Oncology Department, Hospital Clinic, Barcelona, Spain (11) Lead Contact *Correspondence: fathia.mami-chouaib@gustaveroussy.fr
