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1. Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications.

Author

Terrén I, Orrantia A, Astarloa-Pando G, Amarilla-Irusta A, Zenarruzabeitia O, and Borrego F

Subjects
Immunologic Memory, Interleukin-12 pharmacology, Killer Cells, Natural, Cytokines metabolism, Immunity, Innate
Abstract

Natural killer (NK) cells are lymphocytes with a key role in the defense against viral infections and tumor cells. Although NK cells are classified as innate lymphoid cells (ILCs), under certain circumstances they exhibit adaptive and memory-like features. The latter may be achieved, among others, by a brief stimulation with interleukin (IL)-12, IL-15 and IL-18. These cytokine-induced memory-like (CIML) NK cells resemble the trained immunity observed in myeloid cells. CIML NK cells undergo transcriptional, epigenetic and metabolic reprogramming that, along with changes in the expression of cell surface receptors and components of cytotoxic granules, are responsible for their enhanced effector functions after a resting period. In addition, these memory-like NK cells persist for a long time, which make them a good candidate for cancer immunotherapy. Currently, several clinical trials are testing CIML NK cells infusions to treat tumors, mostly hematological malignancies. In relapse/refractory acute myeloid leukemia (AML), the adoptive transfer of CIML NK cells is safe and complete clinical remissions have been observed. In our review, we sought to summarize the current knowledge about the generation and molecular basis of NK cell memory-like responses and the up-to-date results from clinical trials with CIML NK cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Terrén, Orrantia, Astarloa-Pando, Amarilla-Irusta, Zenarruzabeitia and Borrego.)

Published
2022
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2. Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Author

Francisco Borrego, Miguel Genebat, Ane Orrantia, Ezequiel Ruiz-Mateos, Manuel Leal, Joana Vitallé, Leire Gamboa-Urquijo, Laura Tarancon-Diez, Iñigo Terrén, Olatz Zenarruzabeitia, [Vitallé,J, Terrén,I, Gamboa-Urquijo,L, Orrantia,A, Borrego,F, Zenarruzabeitia,O] Biocruces Bizkaia Health Research Institute, Immunopathology Group, Barakaldo, Spain. [Tarancón-Díez,L, Genebat,M, Leal,M, Ruiz-Mateos,E] Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, University of Seville, CSIC, Seville, Spain. [Tarancón-Díez,L] Laboratory of Molecular Immuno-Biology, Gregorio Marañón University Hospital, Health Research Institute, Madrid, Spain. [Leal,M] Internal Medicine Service, Santa Ángela de la Cruz Viamed Hospital, Sevilla, Spain. [Borrego,F] Ikerbasque, Basque Foundation for Science, Bilbao, Spain., This study was supported by a grant from 'Plan Estatal de I+ D+ I 2013–2016, ISCIII-Subdirección de Evaluación y Fomento de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) (Grant PI13/00889)' and Marie Curie Actions, Career Integration Grant, European Commission (Grant CIG 631674). Joana Vitallé and Iñigo Terrén are recipients of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2017_2_0242 and PRE_2018_1_0032). Joana Vitallé and Iñigo Terrén are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB15/008 and FJGB17/003). Laura Tarancón-Díez was supported by Instituto de Salud Carlos III, PFIS (FI00/00431). Olatz Zenarruzabeitia is recipient of a postdoctoral contract funded by 'Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/0128)' and the European Social Fund (ESF)-The ESF invests in your future. Ezequiel Ruiz-Mateos is supported by Programa Nicolás Monardes, C0032-2017, Consejería de Salud y Bienestar Social, Junta de Andalucía. Francisco Borrego is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science., Instituto de Salud Carlos III, European Commission, Eusko Jaurlaritza, Fundación Jesús de Gangoiti Barrera, Junta de Andalucía, and Ikerbasque Basque Foundation for Science

Subjects
0301 basic medicine, Receptor expression, medicine.medical_treatment, T-Lymphocytes, lcsh:Medicine, HIV Infections, CD8-Positive T-Lymphocytes, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Cytotoxic T cell, Receptors, Immunologic, Receptor, lcsh:Science, Cells, Cultured, Multidisciplinary, medicine.diagnostic_test, CD300a receptor, Degranulation, virus diseases, Citocinas, Linfocitos T, 3. Good health, Cytokine, medicine.anatomical_structure, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], 030220 oncology & carcinogenesis, Cytokines, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Cell biology, Anti-HIV Agents, T cell, Immunology, Biology, Article, Flow cytometry, 03 medical and health sciences, Antigens, CD, medicine, Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides [Medical Subject Headings], Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation [Medical Subject Headings], lcsh:R, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings], Péptidos, 030104 developmental biology, Anatomy::Cells::Cells, Cultured [Medical Subject Headings], HIV-1, lcsh:Q, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD [Medical Subject Headings], Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets [Medical Subject Headings], Peptides, CD8, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes [Medical Subject Headings]
Abstract

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response., This study was supported by a grant from “Plan Estatal de I+ D+ I 2013–2016, ISCIII-Subdirección de Evaluación y Fomento de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) (Grant PI13/00889)” and Marie Curie Actions, Career Integration Grant, European Commission (Grant CIG 631674). Joana Vitallé and Iñigo Terrén are recipients of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2017_2_0242 and PRE_2018_1_0032). Joana Vitallé and Iñigo Terrén are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB15/008 and FJGB17/003). Laura Tarancón-Díez was supported by Instituto de Salud Carlos III, PFIS (FI00/00431). Olatz Zenarruzabeitia is recipient of a postdoctoral contract funded by “Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/0128)” and the European Social Fund (ESF)-The ESF invests in your future. Ezequiel Ruiz-Mateos is supported by Programa Nicolás Monardes, C0032-2017, Consejería de Salud y Bienestar Social, Junta de Andalucía. Francisco Borrego is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science.

Published
2020

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