Thor Straten, PerGarrido, Federico2016-07-132016-07-132016-04-19Thor Straten P, Garrido F. Targetless T cells in cancer immunotherapy. J Immunother Cancer. 2016; 4:23http://hdl.handle.net/10668/2269Journal Article;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.enHLA expressionPredictive markersHLA lossImmune evasionCheckpoint inhibitionAdoptive cell transfer (ACT)Antígenos de neoplasiasAtenciónBiomarcadoresLinfocitos T CD8-positivosHumanosInmunoterapiaInmunoterapia adoptivaLinfocitos infiltrantes de tumorLinfocitos T citotóxicosMicroambiente tumoralMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, NeoplasmMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Arousal::AttentionMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, PharmacologicalMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-LymphocytesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::ImmunotherapyMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, AdoptiveMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-InfiltratingMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::T-Lymphocyte Subsets::T-Lymphocytes, CytotoxicMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironmentresearch article27096099open access10.1186/s40425-016-0127-z2051-1426PMC4835921