Dynamic analysis of the immunological response of Balb/c mice with experimental breast cancer submitted to immunotherapy treatment of dendritic cell/ Análise dinâmica da resposta imunológica de camundongos Balb/c com câncer de mama experimental submetido a imunoterapia de células dendríticas

INTRODUCTION: Cancer is a complex disease because it is capable of inhibiting the immune response through tumor escape mechanisms. OBJECTIVE: analyze the dynamics of the immune system during cancer treatment with dendritic cell immunotherapy. We evaluated the presence of tumor infiltrate of CD8 T lymphocytes, transcription factors of CD4 T lymphocytes in the spleen of these animals, the development of tumor volume and the behavior of coestimulatory molecules.  METHODS: 70 female Balb/c mice were divided into experimental and control groups, they were evaluated on the 7th e 14th days after tumor challenge and dendritic cell immunotherapy. RESULTS: Molecules such as T-bet, showed an increased expression in treated tumor group. Our results also demonstrated the higher MFI of CD8 + T lymphocytes infiltrate in the treated groups. Thus, there is a greater MFI of protumoral co-stimulatory molecules such as CTLA4 in the untreated groups. CONCLUSION: the immune system is able to modulate an immune response against tumor within 14 days if the organism is being treated with dendritic cell immunotherapy

Local Lymphocytes and Nitric Oxide Synthase in the Uterine Cervical Stroma of Patients with Grade III Cervical Intraepithelial Neoplasia

OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3), 35.5 (± 9.5), and 50 (± 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05). CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion

Different roles of helper T lymphocytes during dendritic cells vaccine in experimental breast cancer

Breast cancer is the most common women’s tumor. Treatments though effective, are often aggressive and leave the patients vulnerable to developing opportunistic infections. There is a need for less aggressive more effective new therapies. In this study, we have made an attempt to evaluate DCs immunotherapy by flow cytometry, analyzing the presence of infiltrating cells, cytokines and transcription factors in the spleens, lymph nodes and tumors of breast cancer mice undergoing immunotherapy. The 4T1 cell transfection was used to induce breast cancer in Balb/c mice aged 6 to 8 weeks. Mice were treated with 3 doses of DCs vaccine. After the treatment, animals were euthanized, the spleen, lymphnodes and tumors were removed and used to perform flow cytometry. Results have shown higher CD4+ T lymphocytes that produce IL-12 in the spleen of group treated with DCs vaccine (149,8-271,3) 172,4. Further, there was an increase in T-bet (976,1-1075) 1022 in the lymph nodes of tumor group treated with DCs and less FOXP3 (795,7 - 895) 832. Tumoral volume and the FOXP3 were decreased in the treated group. There was an increase in the transcription factor of Th1 profile, and of cytotoxic T lymphocytes, inferring a good immune response. With these observations, it can be concluded that the DC vaccine is effective in combating the development of tumors