Cellular Immunology
The Cellular Immunology Group investigates the mechanisms that regulate immune responses in cancer, autoimmune diseases, and immune tolerance, with the aim of developing new diagnostic and therapeutic strategies.
The group is coordinated by Dra. Aura Muntasell, who leads the cancer immunotherapy research line. Part of the laboratory’s activity is carried out at the Hospital del Mar Research Institute, enabling close integration between basic research and clinical practice.
The group’s research combines basic and translational approaches, using preclinical models and patient samples in close collaboration with hospital clinical services.
"Our goal is to understand and modulate the immune response to improve the diagnosis and treatment of cancer and other immune-mediated diseases"
The main research lines are as follows:
Natural Killer Cells in cancer immunotherapy - Dr. Aura Muntasell
Dr. Aura Muntasell is an Associate Professor in the Department of Cell Biology, Physiology and Immunology. The team has a broad and recognized experience in the study of human Natural Killer (NK) cell biology, involved in the immune response to certain microbial pathogens and tumors.
NK cells can recognize and eliminate transformed cells while facilitating the development of tumor-specific adaptive immunity by shaping the tumor microenvironment through the secretion of pro-inflammatory cytokines. Several mechanisms decreasing NK cell function had been described in cancer patients.
Cancer immunotherapy based on NK cells comprises a range of innovative strategies aimed at harnessing the natural potential of these immune system cells to fight cancer.
Research Lines:
Our current research lines include:
- Immunotherapy to enhance NK cells: Identification of target molecules that, can be leveraged with biological treatments to boost the function of NK lymphocytes in cancer patients.
- NK cells as biomarkers for oncological treatments: Study of NK cells as predictive indicators of response or resistance to treatments, specifically in patients with breast and colon cancer.
- Genetic engineering in NK cells: Development of NK lymphocytes resistant to the suppressive mechanisms of solid tumors as new approaches for adoptive cell therapy for cancer treatment.
- Adoptive cell therapy with NK lymphocytes: Development of protocols to optimize NK lymphocyte-based cancer cell therapy and patient monitoring.
Our research, builds on data from preclinical experimental systems and observational studies in collaboration with the Medical Oncology and Pathology Departments at Hospital del Mar.
Collaborators
Joan Albanell. Head of the Oncology Service of the Hospital del Mar. Head of the Molecular Cancer Therapy Laboratory
Clara Montagut. Coordinator of the Colorectal Cancer Precision Medicine Group
Ana Rovira. Coordinator of the Molecular Cancer Therapy Laboratory
Anna Hernández. Head of the Molecular Cancer Therapy Laboratory
Fabricio Quimis. Laboratory Technician
Mitochondrial dysfunction and autoimmunity. Type 1 diabetes - Dr. Carme Roura-Mir
Lipid autoantigens in human type I diabetes
Insulin-specific autoreactive CD8+ and CD4+ T cells are key to driving the autoimmune response in type 1 diabetes. Other antigenic specificities may be equally important during the development or maintenance of the disease. Most of these proteins reside in the insulin secretory granules or crinophagic bodies of β-cells. There are some reports of MHC class I peptides presented in human T1D. Much less is known about the peptides recognized by CD4+ regulatory or effector T cells in human T1D.
Apart from proteins, lipid-based antigens can be loaded onto non-classical MHC-I CD1 molecules and recognized by NKT cells. Both exogenous and endogenous lipids have been shown to gain access to intracellular compartments and cross-link CD1 molecules. However, the target ligands recognized by these cells in the autoimmune context are barely known. Furthermore, little is known about the local lipid ligands for NKT cells that may be influencing the outcome of the disease. The group is working on two different aspects:
- The regulatory role of iNKT cells in type 1 diabetes
NKT cells regulate effector T cells in an IL13-dependent manner. In patients with T1D, NKT cells appear to lose their regulatory capacity, which may be associated with deficient IL13 production early in the disease. Usero et al. Diabetes 2016;65:2356–66.
The regulatory deficiency of NKT cells in patients with T1D may be related to a differential gene expression pattern compared to NKT cells from healthy controls (ongoing research).
- Lipid-based autoantigens recognized by iNKT cells in T1D
Due to their secretory function, B cells have a highly developed ER and are highly susceptible to ER stress. The group studies whether cellular stress alters the lipid content of B cells by generating lipid antigens that activate iNKT cells.
Response to lipid extracts from b cells
HLA peptides and antigen presentation - Dr. Iñaki Alvarez
The group's work focuses on antigen processing and presentation during the generation of central tolerance in the thymus and in disease. Currently, the group's two main research lines are:
- Study of antigen processing in the class I pathway in the thymus and periphery. The work focuses on analyzing the activity and structure of different types of proteasomes, as well as their contribution to the generation of the immunopeptidome and relevant peptides in cortical thymic epithelial cells (cTECs) and the periphery.
- Analysis of the immunopeptidomes presented by MHC-I and MHC-II molecules during central tolerance and in disease
Information of interest
Advanced Cell therapies for cancer treatment. Aura Muntasell (Investigadora principal). INSTITUTO DE SALUD CARLOS III (PI25/00609). Execució: 01/01/2026-31/12/2028
TAR-NK: A TGF-β- and Activin A-Resistant off-the-shelf NK cell product for cancer treatment. Aura Muntasell (Investigadora Principal). La Caixa Foundation (CI25-20397). Execució:1/09/2025-1/09/2027)
Phase Ib to evaluate safety of TAR-NK cells+cetuximab+irinotecan rechallenge in patients with mCRC (CITRIC-NK). Aura Muntasell Castellvi (Investigadora Principal, IMIM). Proyectos de Investigación Clínica Independiente (ICI) - Instituto de Salud Carlos III (ISCIII), Ref. CI24/00041. Execució: 01/01/25 → 31/12/2028
Dual genetic engineering of NK cells for cancer immunotherapy (DUAL-NK). Aura Muntasell Castellví (Investigadora principal). Convocatòria Consolidación Investigadora. AEI, Ministerio de Ciencia e Innovación. Execució: 1/04/24 → 30/06/26.
Development of a TGF-ß- and Activin A-Resistant off-the-shelf NK cell product for cancer treatment (TAR-NK). Aura Muntasell Castellvi (Investigadora principal). Convocatòria PRODUCTE (Ref. 2024PROD00086) Agència de Gestió d'Ajuts Universitaris de Recerca (AGAUR). Execució: 2/12/24 → 1/06/26.
Novel therapeutic targets for the treatment of APECED. Iñaki Alvarez (Investigador Principal). UAB (PPC2024-38). Execució 16/09/2014-15/03/2026
Paper de les alteracions de la presentació d’antigen mediades per estrès en cèl·lules betai en el desenvolupament de la Diabetis tipus 1. Carme Roura (Investigadora principal). Ministeri Ciència i Innovació, PID2021-125470OB-I00. Execució: 1/09/22 → 28/02/26
Miguel Lopez-Botet, Carlos Vilches, Aura Muntasell. The CD94/NKG2A-HLA-E axis as a target in cancer immunotherapy: a critical perspective. Clin Cancer Res. 2026 Jan 7. doi: 10.1158/1078-0432.CCR-25-0447.
Overcoming TGFβ and activin A suppression boosts NK cell antitumor function. Nat Immunol 26, 540–541 (2025).
Rea, A., Santana-Hernández, S., Villanueva, J. et al. Enhancing human NK cell antitumor function by knocking out SMAD4 to counteract TGFβ and activin A suppression. Nat Immunol (2025).
Santana-Hernández S, Suárez J, Servitja S, Berenguer-Molins P, Costa-Garcia M, Comerma L, Rea A, Perera J, Menéndez S, Arpí O, Bermejo B, Martínez-Larrad MT, Cejalvo JM, Comino-Méndez I, Pascual J, Alba E, López-Botet M, Rojo F, Rovira A, Albanell J, Muntasell A*. NK cell-triggered CCL5/IFNγ-CXCL9/10 axis underlies the clinical efficacy of neoadjuvant anti-HER2 antibodies in breast cancer. J Exp Clin Canc Res 2024; 43(1): 10.
López-Botet M*, De María A, Muntasell A, Della Chiesa M, Vilches C. Adaptive NK cell response to human cytomegalovirus: Facts and open issues. Semin Immunol 2023; 65: 101706.
Cabo M, Santana-Hernández S, Costa-Garcia M, Rea A, Lozano-Rodríguez R, Ataya M, Balaguer F, Juan M, Ochoa MC, Menéndez S, Comerma L, Rovira A, Berraondo P, Albanell J, Melero I, López-Botet M, Muntasell A. CD137 costimulation counteracts TGF? inhibition of NK-cell antitumor function. Cancer Immunol Res 2021; 9(12): 1476-1490.
Noboa-Velástegui J, Valdez-Vega RI, Castro-Albarran J, Madrigal-Ruiz P, Fletes-Rayas A, Ruiz-Quezada S, Ramos-Márquez ME, López-Jiménez JJ, Alvarez I*, Navarro-Hernández R*. Expression of serum and exosomal microRNA-34a in sub-jects with increased fat mass. (2025) Int. J. Mol. Sci. 27:00270. DOI: 10.3390/ijms27010270
Area-Navarro M, Pastor-Moreno A, Scholz E, Cerqueira A, Tirado-Herranz A, Marcilla M, Canals F, Juan M, Palacio JR and Alvarez I. Specific instability of HLA-A*03:01 expression in HEK-293 cells. (2025) Int. J. Mol. Sci. 26:11357. DOI: 10.3390/ijms262311357
Noboa-Velástegui J, León JC, Castro J, Fletes A, Madrigal P, Alvarez I*, Navarro R*. Comparison of methods for isolating exosomes from plasma subjects with normal and high-fat percentages. (2025) Life. 15:410. https://doi.org/10.3390/life15030410
Tirado-Herranz A*, Guasp P*, Pastor-Moreno A, Area-Navarro M, Alvarez I. Analysis of the different subpeptidomes presented by the HLA class I molecules of the B7 supertype. (2023) Cellular Immunology. 387:104707.
Borràs-Tudurí, R., Alcaide, A., Aspeslag, S., Usero, L., Serra, C., Roura-Mir, C., Elewaut, D. & Llebaria, A. New Paradigm in NKT Cell Antigens: MCS-0208 (2-(Hydroxymethyl)phenylthio-phytoceramide) - an Aryl-Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells. (2021) ChemMedChem. 16: 2491.
Funding
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