Journal Article

Dendritic cells combined with tumor cells and α-galactosylceramide induce a potent, therapeutic and NK-cell dependent antitumor immunity in B cell lymphoma

Tellez-Gabriel, Marta, Alvarez-Fernández, Carmen, Escribà-Garcia, Laura, Sierra, Jorge, Briones, Javier

2017

Overview

Background Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation. Methods We evaluated the antitumor effect of a combination of dendritic cells (DCs) and tumor cells with the iNKT cell agonist α-GalCer in a therapeutic model of B cell lymphoma. iNKT, NK and T cell phenotype was determined by flow cytometry. Serum cytokines were analyzed by Luminex technology. Significant differences between survival curves were assessed by the log-rank test. For all other data, Mann–Whitney test was used to analyze the differences between groups. Results This vaccine induced a potent (100% survival), long-lasting and tumor-specific antitumor immune response, that was associated with an increase of both Th1 cytokines and IFN-γ secreting iNKT cells (4.59 ± 0.41% vs. 0.92 ± 0.12% in control group; p = 0.01) and T cells (CD4 IFN-γ + : 3.75 ± 0.59% vs. 0.66 ± 0.18% p = 0.02; CD8 IFN-γ + : 10.61 ± 0.84% vs. 0.47 ± 0.03% p = 0.002). Importantly, natural killer (NK) cells played a critical role in the antitumor effect observed after vaccination. Conclusions This study provides clinically relevant data for the development of iNKT-cell based immunotherapy treatments for patients with B cell malignancies.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adaptive immunity / Animals / Antigens / Antigens, CD1d - metabolism / Antineoplastic Agents - pharmacology / Antitumor activity / B-cell lymphoma / Biomedical and Life Sciences / Biomedicine / Bone marrow / Cancer / Cancer Vaccines - pharmacology / CD1d antigen / CD4 antigen / CD8 antigen / Cell activation / Cell Line, Tumor / Coculture Techniques / Cytokines / Cytokines - metabolism / Dendritic cells / Dendritic Cells - cytology / Dendritic Cells - immunology / Disease Models, Animal / Female / Flow Cytometry / Galactosylceramide / Galactosylceramides - pharmacology / Immune response / Immunobiology and immunotherapy / Immunotherapy / iNKT cells / Killer Cells, Natural - immunology / Laboratory animals / Ligands / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, B-Cell - immunology / Medicine/Public Health / Mice / Mice, Inbred BALB C / Multiple myeloma / Natural killer cells / Phenotype / Rodents / Studies / Survival / T cell receptors / Tumor cells / Tumors / Vaccination