Evidence map›Paper›PMID 41051510›Full record

ArticleCancer immunology, immunotherapy : CII2025

Expression of the inhibitory checkpoints LAG-3, TIM-3, and PD-1 in NK cells and T cells in acute myeloid leukemia: preserved expression of LAG-3 is associated with patient survival.

Isabel Valhondo, Alejandra Pera, Fakhri Hassouneh, Nelson López-Sejas, Pablo Álvarez-Heredia, Juan M Bergua, María José Arcos, Ignacio Casas-Avilés, Joaquín Sánchez-García, Josefina Serrano and 5 more

Abstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Post-translational modifications in CD8Frontiers in immunology · 2026
    Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Isabel ValhondoÁrea de Inmunología, Departamento de Fisiología, Universidad de Extremadura, 10003, Cáceres, Spain.
Alejandra PeraDepartamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, 14004, Córdoba, Spain.
Fakhri HassounehInmunología y Alergia, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004, Córdoba, Spain.
Nelson López-SejasÁrea de Inmunología, Departamento de Fisiología, Universidad de Extremadura, 10003, Cáceres, Spain.
Pablo Álvarez-HerediaInmunología y Alergia, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004, Córdoba, Spain.
Juan M BerguaServicio de Hematología y Hemoterapia, Hospital San Pedro de Alcántara, 10003, Cáceres, Spain.
María José ArcosServicio de Hematología y Hemoterapia, Hospital San Pedro de Alcántara, 10003, Cáceres, Spain.
Ignacio Casas-AvilésServicio de Hematología y Hemoterapia, Hospital San Pedro de Alcántara, 10003, Cáceres, Spain.
Joaquín Sánchez-GarcíaUnidad de Gestión Clínica de Hematología, Hospital Universitario Reina Sofía, 14004, Córdoba, Spain.
Josefina SerranoUnidad de Gestión Clínica de Hematología, Hospital Universitario Reina Sofía, 14004, Córdoba, Spain.
Carmen MartínUnidad de Gestión Clínica de Hematología, Hospital Universitario Reina Sofía, 14004, Córdoba, Spain.
Esther DuránAnatomía y Anatomía Patológica Comparada, Facultad de Veterinaria, Universidad de Extremadura, 10003, Cáceres, Spain.
Corona AlonsoInmunología y Alergia, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004, Córdoba, Spain.
Rafael SolanaDepartamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, 14004, Córdoba, Spain. rsolana@uco.es.
Raquel TarazonaÁrea de Inmunología, Departamento de Fisiología, Universidad de Extremadura, 10003, Cáceres, Spain. rtarazon@unex.es.

Funding

Consejería de Educación, Ciencia y Formación Profesional, Junta de Extremadura, Spain GR21178 and IB20132Instituto de Salud Carlos III PI19/00075Instituto de Salud Carlos III PI21/01125Ministerio de Ciencia e Innovación, Spain SAF2017-87538-RRegional Ministry of Economic Transformation, Industry, Knowledge, and Universities of the Junta de Andalucía DOC_01421Secretaría General de Investigación, Desarrollo e Innovación en Salud, Junta de Andalucía, Spain PECART 0060-2020
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Despite advances in treatment, the average survival rate after diagnosis is low. AML also alters the patient's immune response further contributing to disease progression. The aim of this study was to analyze the expression of LAG-3, TIM-3 and PD-1 inhibitory checkpoints on NK cells and T cells from newly diagnosed AML patients and its impact in patient survival. NK cells and T cells from AML patients showed a lower expression of TIM-3 compared with healthy donors, whereas no significant differences were observed in the expression of LAG-3. The percentages of cells co-expressing these receptors showed a decrease in the percentage of LAG-3 + TIM-3 + PD-1 - NK and T cells from AML patients in comparison with healthy donors. Remarkably, the survival analysis of AML patients according to the expression of these receptors showed that higher expression of LAG-3 on NK cells and T cells was associated with better survival. In addition, those AML patients showing higher co-expression of LAG-3 and TIM-3 on NK and T cells had better survival (higher than 6 months) than those with lower co-expression of LAG-3 and TIM-3, therefore supporting that the expansion of NK and T cells with lower expression of these checkpoint receptors reflects a dysfunctional state associated with poor prognosis. This study identifies the expression of LAG-3 and TIM-3 checkpoints on NK and T cells as potential biomarkers of AML prognosis, contributing to define those patients that could benefit from checkpoint blockade therapies.

Indexed as

Antigens, CDHepatitis A Virus Cellular Receptor 2Killer Cells, NaturalLeukemia, Myeloid, AcuteProgrammed Cell Death 1 ReceptorT-LymphocytesAdultAgedAged, 80 and overBiomarkers, TumorFemaleHumansLymphocyte Activation Gene 3 ProteinMaleMiddle AgedPrognosisAntigens, CDBiomarkers, TumorHAVCR2 protein, humanHepatitis A Virus Cellular Receptor 2Lag3 protein, humanLymphocyte Activation Gene 3 ProteinPDCD1 protein, humanProgrammed Cell Death 1 ReceptorAcute myeloid leukemiaLAG-3NK cellsPD-1T and NKT-like cellsTIM-3

Identifiers

PMID41051510
PMCPMC12500513

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.