Pattern response of dendritic cells in the tumor microenvironment and breast cancer

Abstract

Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development, including malignancy grade and patient prognosis, is influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Among the immune response cells, dendritic cells (DCs) play a key role in the induction and maintenance of anti-tumor responses owing to their unique abilities for antigen cross-presentation and promotion of the activation of specific lymphocytes that target neoplasic cells. However, the tumor microenvironment can polarize DCs, transforming them into immunosuppressive regulatory DCs, a tolerogenic phenotype which limits the activity of effector T cells and supports tumor growth and progression. Various factors and signaling pathways have been implicated in the immunosuppressive functioning of DCs in cancer, and researchers are working on resolving processes that can circumvent tumor escape and developing viable therapeutic interventions to prevent or reverse the expression of immunosuppressive DCs in the tumor microenvironment. A better understanding of the pattern of DC response in patients with BC is fundamental to the development of specific therapeutic approaches to enable DCs to function properly. Various studies examining DCs immunotherapy have demonstrated its great potential for inducing immune responses to specific antigens and thereby reversing immunosuppression and related to clinical response in patients with BC. DCbased immunotherapy research has led to immense scientific advances, both in our understanding of the antitumor immune response and for the treatment of these patients.© 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Breast cancer; Dendritic cells; Tumor microenvironmentCore tip: Breast cancer is a worldwide major public health problem, and dendritic cells are of crucial importance for activating an effective antitumor immune response. Deepening our understanding of the tumor microenvironment can enable the development of new therapies that will make it possible to induce an efficacious antitumor response. Given the search for effective means with which to induce such a response via dendritic cell (DC) immunotherapy, the study of the mechanisms involved in the DC pattern of response in the tumor microenvironment is important.

Tumour-Infiltrating Lymphocytes (TILs) in Breast Cancer: a Predictive or a Prognostic Marker?

“…Moreover, tumour cells can induce direct tolerization of immune effector populations such as CTLs, DCs and NK cells through the secretion of immunosuppressive factors, including prostaglandin E2 (PGE2) and transforming growth factor beta (TGF-β) [60]. Studies have also shown that the tumour microenvironment polarizes DCs, transforming them into immunosuppressive regulatory DCs with a tolerogenic phenotype, which limits effector T cell activities, thereby supporting tumour growth and progression [56,61]. Furthermore, DC numbers and functions can be diminished in breast cancer, with low cell surface expression of CD86 and MHC II as well as low IL-12 secretion demonstrated [62].…”

“…Unfortunately, in the context of breast cancer, tolerance towards TAAs reduces immune recognition and malignant cell clearance, thus facilitating tumour development and metastatic progression [54,55]. Furthermore, tolerance to a particular TAA can be induced via cross-presentation of the antigen by APCs unable to transmit positive co-stimulation [56]. As such, it is evident that cancer cells take advantage of the tolerogenic and immune-evasive processes to escape and evade immune-mediated destruction [51].…”

Role of the Tumor Microenvironment in Breast Cancer

“…Dendritic cells (DC) play an important role in the induction of antitumor responses due to their ability to cross-present antigens to CD4+ and CD8+ T cells, thus activating them to attack neoplastic cells [37]. The maturation of DC depends on the local microenvironment wherein various factors influence the formation of either tolerogenic or immunosuppressive DC [37,38].…”

“…The maturation of DC depends on the local microenvironment wherein various factors influence the formation of either tolerogenic or immunosuppressive DC [37,38]. Tumor-associated stroma shows an abundance of immature DC with impaired capacity to stimulate antitumor immunity [39].…”

Alarmins and Antitumor Immunity

“…As professional APCs, DCs play a critical role in the induction of antitumor responses due to their ability to present antigens to T cells. 128 An effective antitumor immune response by T cells requires efficient antigen presentation by activated mature DCs. The maturation of DCs depends on the local microenvironment and is influenced by various inflammatory stimulants.…”