CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients

NK and CD8+ T cells are the main cytolytic effectors involved in innate and adaptive tumor immune surveillance, respectively. Although their educational pathways differ, similarities in their development and function suggest that CD8+ T lymphocytes could be sensitive to NK cell licensing signals, wh...

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Main Authors: Lourdes Gimeno, Isabel González-Lozano, María F. Soto-Ramírez, María V. Martínez-Sánchez, Pedro López-Cubillana, José L. Fuster, Jerónimo Martínez-García, Jorge Martínez-Escribano, José A. Campillo, Eduardo Pons-Fuster, Belén Ferri, Alicia López-Abad, Manuel Muro, Alfredo Minguela
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:OncoImmunology
Subjects:
Online Access:http://dx.doi.org/10.1080/2162402X.2021.1986943
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author Lourdes Gimeno
Isabel González-Lozano
María F. Soto-Ramírez
María V. Martínez-Sánchez
Pedro López-Cubillana
José L. Fuster
Jerónimo Martínez-García
Jorge Martínez-Escribano
José A. Campillo
Eduardo Pons-Fuster
Belén Ferri
Alicia López-Abad
Manuel Muro
Alfredo Minguela
author_facet Lourdes Gimeno
Isabel González-Lozano
María F. Soto-Ramírez
María V. Martínez-Sánchez
Pedro López-Cubillana
José L. Fuster
Jerónimo Martínez-García
Jorge Martínez-Escribano
José A. Campillo
Eduardo Pons-Fuster
Belén Ferri
Alicia López-Abad
Manuel Muro
Alfredo Minguela
author_sort Lourdes Gimeno
collection DOAJ
description NK and CD8+ T cells are the main cytolytic effectors involved in innate and adaptive tumor immune surveillance, respectively. Although their educational pathways differ, similarities in their development and function suggest that CD8+ T lymphocytes could be sensitive to NK cell licensing signals, which might influence their antitumor response. To demonstrate this hypothesis, we retrospectively evaluated the impact that NK cell licensing interactions have on the expression of CD226 on CD8+ T lymphocytes and on the survival of patients with different hematopoietic and solid cancers (n = 1,023). Prospectively, we analyzed by multiparametric flow cytometry the anti-CD3/CD28-induced proliferation and immune-receptor expression of purified CD8+ T lymphocytes from healthy donors (n = 17) with different combinations of NK cell licensing ligands. Results show that methionine/threonine (M/T) dimorphism at position −21 of the HLA-B leader peptide, but not other HLA class-I dimorphisms involved in the education of NK cells (HLA-C1/C2 or HLA-Bw4), is associated with greater survival and expression of CD226 in cancer patients, which was proportional to the number of methionines present in their genotype. CD8+ T lymphocytes from healthy donors with −21 M showed higher proliferation rates and lower expression of TIGIT after in vitro stimulation. Therefore, CD8+ T lymphocytes, like NK cells, appear to be sensitive to the −21 M/T dimorphism of HLA-B leader peptide, which results in the modulation of CD226 in vivo and the proliferation and expression of TIGIT after in vitro stimulation, all of which could be related to their immune-surveillance capacity and the survival of cancer patients.
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spelling doaj.art-668edbe66e5245d9857e13029114b3422022-12-22T04:04:17ZengTaylor & Francis GroupOncoImmunology2162-402X2021-01-0110110.1080/2162402X.2021.19869431986943CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patientsLourdes Gimeno0Isabel González-Lozano1María F. Soto-Ramírez2María V. Martínez-Sánchez3Pedro López-Cubillana4José L. Fuster5Jerónimo Martínez-García6Jorge Martínez-Escribano7José A. Campillo8Eduardo Pons-Fuster9Belén Ferri10Alicia López-Abad11Manuel Muro12Alfredo Minguela13Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Urology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Oncology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Dermatology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Pathology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Urology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)Immunology Service, Clinic University Hospital Virgen De La Arrrixaca (Hcuva), Biomedical Research Institute of Murcia (Imib)NK and CD8+ T cells are the main cytolytic effectors involved in innate and adaptive tumor immune surveillance, respectively. Although their educational pathways differ, similarities in their development and function suggest that CD8+ T lymphocytes could be sensitive to NK cell licensing signals, which might influence their antitumor response. To demonstrate this hypothesis, we retrospectively evaluated the impact that NK cell licensing interactions have on the expression of CD226 on CD8+ T lymphocytes and on the survival of patients with different hematopoietic and solid cancers (n = 1,023). Prospectively, we analyzed by multiparametric flow cytometry the anti-CD3/CD28-induced proliferation and immune-receptor expression of purified CD8+ T lymphocytes from healthy donors (n = 17) with different combinations of NK cell licensing ligands. Results show that methionine/threonine (M/T) dimorphism at position −21 of the HLA-B leader peptide, but not other HLA class-I dimorphisms involved in the education of NK cells (HLA-C1/C2 or HLA-Bw4), is associated with greater survival and expression of CD226 in cancer patients, which was proportional to the number of methionines present in their genotype. CD8+ T lymphocytes from healthy donors with −21 M showed higher proliferation rates and lower expression of TIGIT after in vitro stimulation. Therefore, CD8+ T lymphocytes, like NK cells, appear to be sensitive to the −21 M/T dimorphism of HLA-B leader peptide, which results in the modulation of CD226 in vivo and the proliferation and expression of TIGIT after in vitro stimulation, all of which could be related to their immune-surveillance capacity and the survival of cancer patients.http://dx.doi.org/10.1080/2162402X.2021.1986943cd8+ t lymphocytesnk cellseducationcd226cancer
spellingShingle Lourdes Gimeno
Isabel González-Lozano
María F. Soto-Ramírez
María V. Martínez-Sánchez
Pedro López-Cubillana
José L. Fuster
Jerónimo Martínez-García
Jorge Martínez-Escribano
José A. Campillo
Eduardo Pons-Fuster
Belén Ferri
Alicia López-Abad
Manuel Muro
Alfredo Minguela
CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients
OncoImmunology
cd8+ t lymphocytes
nk cells
education
cd226
cancer
title CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients
title_full CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients
title_fullStr CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients
title_full_unstemmed CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients
title_short CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients
title_sort cd8 t lymphocytes are sensitive to nkg2a hla e licensing interaction role in the survival of cancer patients
topic cd8+ t lymphocytes
nk cells
education
cd226
cancer
url http://dx.doi.org/10.1080/2162402X.2021.1986943
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