Dados do Resumo

Título

ANALYSIS OF THE FUNCTIONAL PROFILE OF DENDRITIC CELLS USED IN THE IMMUNOTHERAPY OF BREAST CANCER INDUCED BY 4T1 CELLS IN BALB/C MICE

Introdução

Dendritic cell (DC)-based immunotherapy has significant potential to modulate specific anti-tumor immune responses, particularly by enhancing T-cell activity against tumors. Although the function of these cells as potent antigen presenters is well established, the cytotoxic role of DCs, especially in the context of breast cancer immunotherapy, requires further investigation.

Objetivo

To investigate the fate and function of DCs in breast cancer immunotherapy and to elucidate the direct or indirect effector mechanisms of these cells in the elimination of tumor cells.

Métodos

38 female BALB/c mice (CEUA/UFTM 23085.010271/2022-08) were divided into a tumor control group (n=12) and an immunotherapy treated group (n=12). The remaining 14 animals were used for immunotherapy preparation. Tumor induction was performed with 4T1 cells, analogous to triple-negative breast cancer cells in women. After tumor induction, the treated group received one dose of immunotherapy with CFSE-labeled DCs. DC migration was monitored using the in vivo MS FX PRO device. After euthanasia, immunofluorescence staining was performed on histological sections of lymph nodes for MHC-II (I-A), CD4+ T lymphocytes and CD8+ T lymphocytes to elucidate the antigen presentation process, and on histological sections of tumors for granzyme B, perforin, Fas and FasL to assess cytotoxicity. Statistical analysis was performed using GraphPad 9 software with a significance level of p<0.05.

Resultados

Immunofluorescence analyses showed that DCs administered in the immunotherapy preferentially migrated to the lymph nodes and performed their function of antigen presentation. Regarding the cytotoxic effect of DCs on tumors, a significant reduction in the expression of granzyme B, perforin and Fas was observed in tumors of treated animals compared to untreated animals. On the other hand, an increase in the expression of FasL was observed in the treated group. In addition, a reduction in tumor volume was observed, suggesting that this reduction was not exclusively due to granzyme B and perforin, but also to the modulation of Fas and FasL in the tumors of the treated animals.

Conclusões

The results indicate that in the model studied, DCs derived from immunotherapy not only efficiently presented antigens, but also contributed to the anti-tumor cytotoxic response, strengthening their therapeutic potential in the treatment of breast cancer.

Financiador do resumo

FAPEMIG

Palavras Chave

Dendritic cell; Breast cancer; immunotherapy