KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
| Autor: | Jerónimo Martínez-García, Emilio M. Serrano-López, Jorge A. Martínez-Escribano, María D. Martínez-Hernández, María V. Martínez-Sánchez, Alfredo Minguela, Senena Corbalán-García, Francisco García-Cózar, Lourdes Gimeno, María A. Cánovas-Zapata, María F Soto-Ramírez, María R. Álvarez-López, O. S. Acuña, Pedro López-Cubillana, José A. Campillo |
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| Přispěvatelé: | Biomedicina, Biotecnología y Salud Pública, [Gimeno,L, Campillo,JA, Cánovas-Zapata,MA, Martínez-Sánchez,MV, Martínez-Hernández,MD, Soto-Ramírez,MF, Álvarez-López,MR, Minguela,A] Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Gimeno,L] Human Anatomy Department, University of Murcia (UM), Murcia, Spain. [Serrano-López,EM, Corbalan-García,S] Department of Biochemistry and Molecular Biology, Veterinary School, International Excellence Campus 'Campus Mare Nostrum', Universidad Murcia, Murcia, Spain. [Serrano-López,EM, Corbalan-García,S] Biomembranes and Cell Signaling, Instituto Murciano de Investigación Biomédica, Murcia, Spain. [Acuña,OS] Faculty of Veterinary and Zootechnics, Autonomous University of Sinaloa (UAS), Culiacan, Mexico. [Acuña,OS] Department of Research, Animal Reproduction Biotechnology (ARBiotech), Culiacan, Mexico. [García-Cózar,F] Department of Biomedicine, Biotechnology and Public Health (Immunology), University of Cadiz and Institute of Biomedical Research Cádiz (INIBICA), Cadiz, Spain. [López-Cubillana,P] Urology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Martínez-Escribano,J] Dermatology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Martínez-García,J] Oncology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Álvarez-López,MR] Faculty of Health Sciences, Universidad Católica San Antonio de Murcia, UCAM, Murcia, Spain., This research was funded by the Spanish Ministry of Economy—Institute of Health Carlos III (PI1302297), Fundación Mutua Madrileña (AP74392010), and Fundación Séneca de la Agencia de Ciencia y Tecnología, Región de Murcia, (20812-PI-18). M.V. Martínez-Sánchez was funded by the Asociación Pablo Ugarte (APU). |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research immunosurveillance Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Monitoring Physiologic::Monitoring Immunologic [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine Cytotoxic T cell Vigilancia inmunológica Linfocitos T lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Neoplasias CD8+T cells KIR Immunosurveillance medicine.anatomical_structure Oncology Tumor microenvironment 030220 oncology & carcinogenesis Análisis de secuencia por matrices de oligonucleótidos microarray T cell Cells chemical and pharmacologic phenomena Biology CD8+ T cells lcsh:RC254-282 Article Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription Genetic::Transcriptome [Medical Subject Headings] 03 medical and health sciences T Lymphocytes Immune system KIR2DL1 Células Microambiente tumoral medicine cancer Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies [Medical Subject Headings] Diseases::Neoplasms::Neoplasms by Histologic Type::Nevi and Melanomas::Melanoma [Medical Subject Headings] Receptores KIR Cancer Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [Medical Subject Headings] CD8+T medicine.disease Gene expression profiling 030104 developmental biology Cancer research gene expression CD8 Expresión génica Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes [Medical Subject Headings] |
| Zdroj: | Cancers 2020, 12(10), 2991 RODIN. Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz instname RODIN: Repositorio de Objetos de Docencia e Investigación de la Universidad de Cádiz Universidad de Cádiz Cancers, Vol 12, Iss 2991, p 2991 (2020) Cancers Volume 12 Issue 10 |
| Popis: | Simple Summary Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved. Abstract Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved. |
| Databáze: | OpenAIRE |
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