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Cited by 17Immune Cell Function and InteractionCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

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Gimeno, Lourdes, Serrano-López, Emilio M., Campillo, José A., Cánovas-Zapata, María A., Acuña, Omar S., García-Cózar, Francisco, Martínez-Sánchez, María V., Martínez-Hernández, María D. +7 more·2020·Cancers
DOI 10.3390/cancers12102991PMC PMC7650600
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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.

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  • CD8+ T cells showing high expression levels of KIRs are reported in peripheral blood of cancer patients.

    “CD8+ T cells showing high expression levels of KIRs are also reported in peripheral blood of cancer patients”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [51]

    The Conclusions report that KIR-expressing CD8+ T cells accumulate in the peripheral blood of cancer patients. However, Methods §4.2 measures KIR expression as the percentage of positive cells, not the level of KIR expression on individual cells, so the claim’s “high expression levels” is not established. (LLM, conf=0.86)

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Authors
Gimeno, L., Serrano-López, E. M., Campillo, J. A., Cánovas-Zapata, M. A., Acuña, O. S., García-Cózar, F., Martínez-Sánchez, M. V., Martínez-Hernández, M. D., Soto-Ramírez, M. F., López-Cubillana, P., Martínez-Escribano, J., Martínez-García, J., Corbalan-García, S., Álvarez-López, M. R., & Minguela, A.
Affiliations
  • Instituto Murciano de Investigación Biosanitaria (ES)
  • Universidad de Murcia (ES)
  • Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), 30120 Murcia, Spain
  • Universidad Autónoma de Sinaloa (MX)
  • Department of Biomedicine, Biotechnology and Public Health (Immunology), University of Cadiz and Institute of Biomedical Research Cádiz (INIBICA), 11009 Cadiz, Spain
  • Dermatology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), 30120 Murcia, Spain
  • Department of Biochemistry and Molecular Biology, Veterinary School, International Excellence Campus “Campus Mare Nostrum”, Universidad Murcia, 30100 Murcia, Spain
Corresponding author
Minguela, Alfredo
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2020-10-15
Volume
12
Issue
10
Pages
2991
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers12102991
PMC
PMC7650600
OpenAlex
W3093284555
Cited by
17
References
1
Citations by year
2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 2
FWCI
0.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • RODIN (Universidad de Cádiz) (submittedVersion, cc-by)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
Funders
  • Instituto de Salud Carlos III (PI1302297)
  • Fundación Mutua Madrileña (AP74392010)
  • Fundación Séneca (20812-PI-18)
  • Asociación Pablo Ugarte (APU) ((no number))
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
killer cell immunoglobulin-like receptors, tumor surveillance, KIR2DL1, melanoma, bladder cancer, ovarian cancer, overall survival, gene expression profiling, tumor microenvironment, T cell expansion

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