Dados do Resumo

Título

Optimizing Dendritic Cell-Based Immunotherapy: Comparative Efficacy in Tumor Reduction and Metastatic Control

Introdução

The versatility of dendritic cells (DCs) makes them powerful tools in the development of personalized cancer immunotherapies. By precisely engineering the immune response, DCs vaccines can potentiate the elimination of tumor cells, including metastases in organs such as lungs. The plasticity of DCs is influenced by the stimuli and microenvironment in which they are introduced, making immunotherapy a promising strategy in the direct fight against breast cancer and its secondary complications.

Objetivo

To evaluate the efficiency of DCs maturation protocols for immunotherapy in an experimental model of breast carcinoma induced by 4T1 cells, by analyzing tumor volume, pulmonary metastatic area, pulmonary infiltrate of helper (CD4+) and cytotoxic (CD8+) T lymphocytes, and tumor infiltrate of CD4+ and CD8+ T lymphocytes.

Métodos

According to CEUA-UFTM guidelines n°23085.005932/2022-75, 54 female Balb/c mice were divided into control group (CG,n=6), with animals without interventions, tumor group (TG,n=12), with tumor-induced and untreated mice, protocol 1 group (P1G,n=12), treated with conventional protocol immunotherapy (TNF-α), and protocol 2 group (P2G,n=12), treated with alternative protocol immunotherapy (TNF-α, IL-12 and RANTES). An additional 12 mice provided bone marrow for immunotherapy doses. After 21 days of tumor induction and subsequent treatment, all animals were euthanized. A portion of the lungs was used to prepare histologic slides stained with hematoxylin and eosin (HE) to quantify metastases, and another portion of these organs, as well as the tumors, was analyzed by flow cytometry with markers for CD4+ and CD8+ T lymphocytes. Statistical analysis was performed using GraphPad Prism 8.0 software with a significance level of p<0.05.

Resultados

Upon analysis of the tumor volumes, it was observed that the group subjected to the alternative protocol exhibited a more pronounced reduction in tumor growth. However, this difference was not statistically significant when compared to the other groups. Furthermore, the HE staining analyses indicated that the areas of lung metastases in the P2G animals were smaller in comparison to the TG (p=0.001). However, this difference was also not statistically significant when compared to P1G (p=0.91). These findings were corroborated by the flow cytometry data, which demonstrated a significantly greater infiltration of CD8+ T in the lung tissue of the P2G animals compared to the CG (p<0.0001) and P1G (p<0.0001). Furthermore, there was a notable increase in the presence of CD4+ T within the tumors of the same animals, in comparison to the TG (p<0.0001) and P1G (p<0.0001).

Conclusões

The results show that it is possible to modulate the anti-tumor immune response through the maturation process of DCs for immunotherapy, achieving significant results in reducing tumor volume and lung metastases. The efficacy of the different maturation protocols highlights the importance of optimizing these strategies to achieve more robust and targeted immune responses. These results open up perspectives for future studies exploring the application of DCs immunotherapy in different cancer types and with diverse patterns of organotropism for metastasis.

Financiador do resumo

FAPEMIG

Palavras Chave

immunotherapy; Dendritic cells; Alternative Maturation Protocol