RESUMO
BACKGROUND: Tumor microenvironment is infiltrated by many immune cells, of which Regulatory T (Treg) cells are usually considered as negative regulators of the immune responses. However, the effect of FOXP3+ (forkhead box transcription factor 3) Treg cells infiltrated into the tumor areas on the prognosis of breast cancer is controversial. This meta-analysis aimed to dissect the potential values of FOXP3+ tumor-infiltrating lymphocytes (TILs) as a prognosis predictor of breast cancer. METHODS: After systematic retrieval of all relevant studies, 28 eligible articles were identified for meta-analysis. Odd ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) were obtained for pooled analyses of pathological complete response (pCR), overall survival (OS), and corresponding forest plots and funnel plots were plotted, respectively. RESULTS: Pooled results revealed that patients with higher levels of FOXP3+ TILs experienced better pCR (OR: 1.24, 95% CI 1.09-1.41) and OS (HR: 0.79, 95% CI 0.64-0.97). Subgroup analysis revealed that elevated FOXP3+ TILs were significantly associated with improved pCR (OR: 1.20, 95% CI 1.02-1.40) and OS (HR: 0.22, 95% CI 0.06-0.88) in human epidermal growth factor receptor 2 positive (HER2+) breast cancer patients. Furthermore, FOXP3+ TILs in the stromal area were statistically correlated with the favorable pCR (OR: 1.22, 95% CI 1.08-1.38) and OS (HR: 0.68, 95% CI 0.49-0.96). CONCLUSIONS: The predictive role of FOXP3+ TILs in the prognosis of breast cancer is influenced by various factors such as molecular subtype of breast cancer and the location of Treg. In HER2+ breast cancer and triple-negative breast cancer, FOXP3+ TILs are associated with better pCR and OS. Additionally, FOXP3+ TILs in stromal represent a favourable prognosis.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Linfócitos T Reguladores/patologia , Fatores de Transcrição Forkhead/metabolismo , Microambiente TumoralRESUMO
This review addresses the role of regulatory T cells (Tregs), which are essential for maintaining peripheral tolerance and controlling pathogen immunity, in the host response against Paracoccidioides brasiliensis, a primary fungal pathogen. A brief introduction on the general features of Treg cells summarizes their main functions, subpopulations, mechanisms of suppression and plasticity. The main aspects of immunity in the diverse forms of the P. brasiliensis infection are presented, as are the few extant studies on the relevance of Treg cells in the control of severity of the human disease. Finally, the influence of Toll-like receptors, Dectin-1, NOD-like receptor P3 (NLRP3), Myeloid differentiation factor-88 (MyD88), as well as the enzyme indoleamine 2,3 dioxygenase (IDO) on the expansion and function of Treg cells in a murine model of pulmonary paracoccidioidomycosis (PCM) is also discussed. It is demonstrated that some of these components are involved in the negative control of Treg cell expansion, whereas others positively trigger the proliferation and activity of these cells. Finally, the studies here summarized highlight the dual role of Treg cells in PCM, which can be protective by controlling excessive immunity and tissue pathology but also deleterious by inhibiting the anti-fungal immunity necessary to control fungal growth and dissemination.