Integrated Immune Profiling Identifies Treatment-Associated Immune Patterns in Patients with B-Cell Hematological Malignancies.
11 affiliations
- 1Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC-University of Salamanca), Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37008Salamanca, Spain.
- 2Instituto de Investigación Biomédica de Salamanca(IBSAL), Complejo Asistencial de Salamanca, Paseo de San Vicente, 58, 37008Salamanca, Spain.
- 3Plataforma de Proteómica Clínica, Instituto de Investigación Biomédica de Salamanca, (IBSAL), 37007Salamanca, Spain.
- 4Mucosal Immunology Lab, Institute of Biomedicine and Molecular Genetics (IBGM, University of Valladolid-CSIC), 47003Valladolid, Spain.
- 5Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, 28029Madrid, Spain.
- 6Flow Cytometry Facility, Institute of Biomedicine and Molecular Genetics (IBGM, University of Valladolid-CSIC), 47003Valladolid, Spain.
- 7Internal Medicine Department, Hospital Clínico Universitario de Valladolid, 47003Valladolid, Spain.
- 8Department of Hematology, Hospital Clínico Universitario de Valladolid, 47003Valladolid, Spain.
- 9Instituto de Investigación Biosanitaria de Valladolid (IBioVall), 47010Valladolid, Spain.
- 10Centro de Investigaciones Biomédicas en Red de Enfermedades Infecciosas (CIBERINFEC), 28029Madrid, Spain.
- 11Department of Pharmaceutical Sciences, Organic Chemistry, Faculty of Pharmacy, University of Salamanca, CIETUS, IBSAL, 37007Salamanca, Spain.
Abstract
Immune dysfunction in hematological malignancies arises from both disease-related alterations and therapeutic interventions, yet comprehensive approaches for characterizing the immune status remain limited. We evaluated an integrated immune profiling strategy combining antigen-specific serology and high-dimensional B-cell phenotyping. Thirty-eight patients with B-cell hematological malignancies receiving ibrutinib-, lenalidomide-, and rituximab-based therapies, or no treatment, were analyzed. Antigen-specific humoral responses were assessed by using a customized protein microarray containing 37 microbial antigens, enabling parallel IgG and IgM profiling. B-cell subpopulations were characterized by spectral flow cytometry. Multiomics factor analysis was applied to integrate serological and cellular data sets and identify major sources of immune variability. Distinct serological and cellular immune profiles were observed across therapeutic groups. Patients receiving ibrutinib displayed lower IgG levels against several microbial antigens and alterations in multiple B-cell compartments, whereas patients receiving lenalidomide-based therapy showed comparatively preserved B-cell populations and broader antigen-specific IgG reactivity. Rituximab-containing regimens were associated with marked reductions in several B-cell subsets. Integrated analysis identified cellular immune features as the major contributors to interpatient heterogeneity, which suggests the presence of treatment-associated immune patterns within the studied cohort. Therefore, integrated serological and cellular profiling provides a scalable framework for characterizing an immune fingerprint with potential prognostic value in patients with B-cell hematological malignancies. These findings support further investigation of immune monitoring approaches in larger longitudinal cohorts.
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BibTeX
@article{ariashidalgo2026integrated,
title = {{Integrated Immune Profiling Identifies Treatment-Associated Immune Patterns in Patients with B-Cell Hematological Malignancies.}},
author = {Carlota Arias-Hidalgo and Juan Hernández-Vazquez and Cristina Teodosio and Pablo Juanes-Velasco and Ana Nuño-Soriano and Paloma Cal-Sabater and Elisa Arribas-Rodríguez and Aida Fiz-López and Marina Pérez-Mazzali and Álvaro Martín-Muñoz and Pablo Tellería and Marina G De Vicuña and Javier Gamazo-Herrero and Ignacio de la Fuente-Graciani and Sonia Pérez-González and Sara Bravo and Cristina García-Alonso and Carlos Dueñas and María Jesús Peñarrubia and Manuel Vigo-Aceves and Claudia Núñez-Abascal and Lucía Neira-González and Rafael Gongora and Sara Cuesta-Sancho and David Bernardo and Ángela-Patricia Hernández and Manuel Fuentes},
journal = {Journal of proteome research},
year = {2026},
month = oct,
doi = {10.1021/acs.jproteome.6c00394},
url = {https://europepmc.org/article/MED/42918109},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated Immune Profiling Identifies Treatment-Associated Immune Patterns in Patients with B-Cell Hematological Malignancies.
AU - Carlota Arias-Hidalgo
AU - Juan Hernández-Vazquez
AU - Cristina Teodosio
AU - Pablo Juanes-Velasco
AU - Ana Nuño-Soriano
AU - Paloma Cal-Sabater
AU - Elisa Arribas-Rodríguez
AU - Aida Fiz-López
AU - Marina Pérez-Mazzali
AU - Álvaro Martín-Muñoz
AU - Pablo Tellería
AU - Marina G De Vicuña
AU - Javier Gamazo-Herrero
AU - Ignacio de la Fuente-Graciani
AU - Sonia Pérez-González
AU - Sara Bravo
AU - Cristina García-Alonso
AU - Carlos Dueñas
AU - María Jesús Peñarrubia
AU - Manuel Vigo-Aceves
AU - Claudia Núñez-Abascal
AU - Lucía Neira-González
AU - Rafael Gongora
AU - Sara Cuesta-Sancho
AU - David Bernardo
AU - Ángela-Patricia Hernández
AU - Manuel Fuentes
PY - 2026
DA - 2026/10/01
JO - Journal of proteome research
DO - 10.1021/acs.jproteome.6c00394
UR - https://europepmc.org/article/MED/42918109
AB - Immune dysfunction in hematological malignancies arises from both disease-related alterations and therapeutic interventions, yet comprehensive approaches for characterizing the immune status remain limited. We evaluated an integrated immune profiling strategy combining antigen-specific serology and high-dimensional B-cell phenotyping. Thirty-eight patients with B-cell hematological malignancies receiving ibrutinib-, lenalidomide-, and rituximab-based therapies, or no treatment, were analyzed. Antigen-specific humoral responses were assessed by using a customized protein microarray containing 37 microbial antigens, enabling parallel IgG and IgM profiling. B-cell subpopulations were characterized by spectral flow cytometry. Multiomics factor analysis was applied to integrate serological and cellular data sets and identify major sources of immune variability. Distinct serological and cellular immune profiles were observed across therapeutic groups. Patients receiving ibrutinib displayed lower IgG levels against several microbial antigens and alterations in multiple B-cell compartments, whereas patients receiving lenalidomide-based therapy showed comparatively preserved B-cell populations and broader antigen-specific IgG reactivity. Rituximab-containing regimens were associated with marked reductions in several B-cell subsets. Integrated analysis identified cellular immune features as the major contributors to interpatient heterogeneity, which suggests the presence of treatment-associated immune patterns within the studied cohort. Therefore, integrated serological and cellular profiling provides a scalable framework for characterizing an immune fingerprint with potential prognostic value in patients with B-cell hematological malignancies. These findings support further investigation of immune monitoring approaches in larger longitudinal cohorts.
SN - 1535-3893
SN - 1535-3907
ER -