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Title: Targetless T cells in cancer immunotherapy.
Authors: Thor Straten, Per
Garrido, Federico
metadata.dc.contributor.authoraffiliation: [Thor Staten,P] Department of Hematology, Centre for Cancer Immune Therapy (CCIT), Copenhagen University Hospital, Herlev, Denmark. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. [Garrido,F] Servicio de Analisis Clinicos e Inmunologia, UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves, Granada, Spain. Instituto de Investigacion Biosanitaria IBS, Granada, Spain. Departamento de Bioquimica, Biologia Molecular e Inmunologia III, Universidad de Granada, Granada, Spain.
Keywords: HLA expression;Predictive markers;HLA loss;Immune evasion;Checkpoint inhibition;Adoptive cell transfer (ACT);Antígenos de neoplasias;Atención;Biomarcadores;Linfocitos T CD8-positivos;Humanos;Inmunoterapia;Inmunoterapia adoptiva;Linfocitos infiltrantes de tumor;Linfocitos T citotóxicos;Microambiente tumoral
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Neoplasm
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Arousal::Attention
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-Infiltrating
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::T-Lymphocyte Subsets::T-Lymphocytes, Cytotoxic
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment
Issue Date: 19-Apr-2016
Publisher: BioMed Central
Citation: Thor Straten P, Garrido F. Targetless T cells in cancer immunotherapy. J Immunother Cancer. 2016; 4:23
Abstract: Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell transfer (ACT) using expanded tumor infiltrating lymphocytes (TIL) or genetically modified cytotoxic T cells. However, despite clear clinical responses, only a fraction of patients respond to treatment and there is an urgent call for characterization of predictive biomarkers. CD8 positive T cells can infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells. It is therefore mandatory to explore if these important molecules for T cell cytotoxicity are expressed by cancer target cells. We have indications that different types of immunotherapy can modify the tumor microenvironment and up-regulate reduced HLA class I expression in cancer cells but only if the associated molecular mechanisms is reversible (soft). However, in case of structural (hard) aberrations causing HLA class I loss, tumor cells will not be able to recover HLA class I expression and as a consequence will escape T-cell lysis and continue to growth. Characterization of the molecular mechanism underlying the lack or downregulation of HLA class I expression, seems to be a crucial step predicting clinical responses to T cell mediated immunotherapy, and possibly aid the selection of strategies that could condition patients for response. Thus, characterization of HLA expression by cancer cells could therefore represent an important predictive marker for immunotherapy of cancer.
Description: Journal Article;
metadata.dc.identifier.doi: 10.1186/s40425-016-0127-z
ISSN: 2051-1426 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de las Nieves
01- Artículos - ibsGRANADA. Instituto de Investigación Biosanitaria de Granada

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