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Dendritic cell-based immunotherapy modulates the systemic inflammatory profile in a 4T1 breast cancer model
Tauana Christina Dias1,2, Jéssica Ferreira Vieira1, Katiane Tostes2
1Oncology Research Institute (Instituto de Pesquisa em Oncologia, IPON), Federal University of the Triângulo Mineiro (Universidade Federal do Triângulo Mineiro, UFTM), Uberaba 38025-350, Minas Gerais, Brazil.
Aim:
Breast cancer remains a major cause of cancer-related mortality in women, particularly in advanced stages where therapeutic options are limited. While immune checkpoint inhibitors (ICIs) have improved outcomes in a subset of patients, many do not respond, highlighting the need for alternative immunotherapeutic strategies. This study evaluated the effect of dendritic cell (DC)-based immunotherapy on tumor growth and on the inflammatory profile of peritoneal myeloid cells in a 4T1 murine breast cancer model.
Methods:
BALB/c mice bearing 4T1 breast tumors were treated with bone marrow-derived DC-based immunotherapy. Tumor volume was monitored over time, and CD14+ cells obtained from peritoneal lavage were analyzed by flow cytometry for the cytokines IL-12, IL-17, and TNF-α and the transcription factors RORγT and GATA3.
Results:
DC-based immunotherapy was associated with a non-significant trend toward reduced tumor volume and a marked suppression of key proinflammatory cytokines: IL-12 (P < 0.0005), IL-17 (P < 0.0001), and TNF-α (P < 0.0001). Expression of the transcription factors RORγT and GATA3, associated with Th17 and Th2 differentiation, was also downregulated (P < 0.0001). These immunological effects were observed in CD14+ myeloid cells from the peritoneal compartment.
Conclusions:
DC-based immunotherapy modulates the systemic/peritoneal inflammatory profile and attenuates tumor-promoting inflammation. This strategy may offer therapeutic benefit for patients with breast cancer who are unresponsive to conventional or ICI-based treatments and supports its further evaluation in translational studies.
