Targetless T cells in cancer immunotherapy
| Autor: | Per thor Straten, Federico Garrido |
|---|---|
| Přispěvatelé: | [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., Grant sponsor: Instituto de Salud Carlos III [FEDER Funds (EU)], Grant numbers: PI 14/01978, PT 13/0010/0039. Grant sponsor: Junta de Andalucía, Grant number: CTS-143, Danish Cancer Society, The Danish Council for Independent Research, The Daniel Foundation, The Toyota Foundation. |
| Jazyk: | angličtina |
| Předmět: |
Atención
0301 basic medicine Cancer Research Adoptive cell transfer medicine.medical_treatment Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Cell therapy 0302 clinical medicine Cancer immunotherapy Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes Mononuclear::Lymphocytes::Lymphocytes Tumor-Infiltrating [Medical Subject Headings] Checkpoint inhibition Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [Medical Subject Headings] Immunology and Allergy Cytotoxic T cell Linfocitos T CD8-positivos Immune evasion Tumor antigen Humanos medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Molecular Medicine Linfocitos T citotóxicos Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers Pharmacological [Medical Subject Headings] Adoptive cell transfer (ACT) T cell Immunology Inmunoterapia adoptiva Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes Mononuclear::Lymphocytes::Lymphocyte Subsets::T-Lymphocyte Subsets::T-Lymphocytes Cytotoxic [Medical Subject Headings] Predictive markers Linfocitos infiltrantes de tumor 03 medical and health sciences Microambiente tumoral Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Arousal::Attention [Medical Subject Headings] medicine Inmunoterapia Antigen-presenting cell Pharmacology HLA expression Tumor-infiltrating lymphocytes business.industry Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [Medical Subject Headings] Chemicals and Drugs::Biological Factors::Antigens::Antigens Neoplasm [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] Antígenos de neoplasias HLA loss Biomarcadores 030104 developmental biology Commentary business Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes [Medical Subject Headings] |
| Zdroj: | Journal for Immunotherapy of Cancer thor Straten, E P & Garrido, F 2016, ' Targetless T cells in cancer immunotherapy ', Journal for ImmunoTherapy of Cancer, vol. 4, no. 1, 23 . https://doi.org/10.1186/s40425-016-0127-z |
| ISSN: | 2051-1426 |
| DOI: | 10.1186/s40425-016-0127-z |
| Popis: | Journal 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. Yes |
| Databáze: | OpenAIRE |
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