Person:
Pérez Alenza, María De Los Dolores

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First Name
María De Los Dolores
Last Name
Pérez Alenza
URI
https://hdl.handle.net/20.500.14352/80397
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Medicina y Cirugía Animal
Area
Medicina y Cirugía Animal
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Author: Alonso Díez, Ángela ×

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    Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity
    (International Journal of Molecular Sciences, 2023) Barreno San Antolín, Lucía; Sevane Fernández, Natalia; Valdivia Lara, Edgar Guillermo; Alonso Miguel, Daniel; Suárez Redondo, María; Alonso Díez, Ángela; Fiering, Steven; Beiss, Veronique; Steinmetz, Nicole F.; Pérez Alenza, María De Los Dolores; Peña Fernández, Laura Luisa
    Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.
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    Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
    (Cells, 2023) Valdivia Lara, Edgar Guillermo; Alonso Miguel, Daniel; Pérez Alenza, María De Los Dolores; Zimmermann, Anna Barbara Emilia; Schaafsma, Evelien; Kolling IV, Fred W.; Barreno San Antolín, Lucía; Alonso Díez, Ángela; Beiss, Veronique; Affonso de Oliveira, Jessica Fernanda; Suárez Redondo, María; Fiering, Steven; Steinmetz, Nicole F.; Vom Berg, Johannes; Peña Fernández, Laura Luisa; Arias Pulido, Hugo
    The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.