title: From T cell "exhaustion" to anti-cancer immunity.
abstract: The immune system has the potential to protect from malignant diseases for extended periods of time. Unfortunately, spontaneous immune responses are often inefficient. Significant effort is required to develop reliable, broadly applicable immunotherapies for cancer patients. A major innovation was transplantation with hematopoietic stem cells from genetically distinct donors for patients with hematologic malignancies. In this setting, donor T cells induce long-term remission by keeping cancer cells in check through powerful allogeneic graft-versus-leukemia effects. More recently, a long awaited breakthrough for patients with solid tissue cancers was achieved, by means of therapeutic blockade of T cell inhibitory receptors. In untreated cancer patients, T cells are dysfunctional and remain in a state of T cell "exhaustion". Nonetheless, they often retain a high potential for successful defense against cancer, indicating that many T cells are not entirely and irreversibly exhausted but can be mobilized to become highly functional. Novel antibody therapies that block inhibitory receptors can lead to strong activation of anti-tumor T cells, mediating clinically significant anti-cancer immunity for many years. Here we review these new treatments and the current knowledge on tumor antigen-specific T cells.
authors.affiliation: Ludwig Cancer Research Center and Department of Oncology, Clinical Tumor Biology & Immunotherapy Group, Lausanne University Hospital Center (CHUV) and University of Lausanne, Route de la Corniche 9A, CH-1066 Epalinges, Switzerland.
authors.forename: Grégory
authors.initials: G
authors.lastname: Verdeil
authors.affiliation: Ludwig Cancer Research Center and Department of Oncology, Clinical Tumor Biology & Immunotherapy Group, Lausanne University Hospital Center (CHUV) and University of Lausanne, Route de la Corniche 9A, CH-1066 Epalinges, Switzerland.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: Fuertes Marraco
authors.affiliation: Ludwig Cancer Research Center and Department of Oncology, Clinical Tumor Biology & Immunotherapy Group, Lausanne University Hospital Center (CHUV) and University of Lausanne, Route de la Corniche 9A, CH-1066 Epalinges, Switzerland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Murray
authors.affiliation: Ludwig Cancer Research Center and Department of Oncology, Clinical Tumor Biology & Immunotherapy Group, Lausanne University Hospital Center (CHUV) and University of Lausanne, Route de la Corniche 9A, CH-1066 Epalinges, Switzerland. Electronic address: doc@dspeiser.ch.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D000818:Animals; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
keywords: Cancer biology; Cancer immunotherapy; Clinical trials; Exhaustion; T cells; Tumor microenvironment