The significant role of mast cells in cancer

Abstract

Mast cells (MC) are a bone marrow-derived, long-lived, heterogeneous cellular population that function both as positive and negative regulators of immune responses. They are arguably the most productive chemical factory in the body and influence other cells through both soluble mediators and cell-to-cell interaction. MC are commonly seen in various tumors and have been attributed alternatively with tumor rejection or tumor promotion. Tumor-infiltrating MC are derived both from sentinel and recruited progenitor cells. MC can directly influence tumor cell proliferation and invasion but also help tumors indirectly by organizing its microenvironment and modulating immune responses to tumor cells. Best known for orchestrating inflammation and angiogenesis, the role of MC in shaping adaptive immune responses has become a focus of recent investigations. MC mobilize T cells and antigen-presenting dendritic cells. They function as intermediaries in regulatory T cells (Treg)-induced tolerance but can also modify or reverse Treg-suppressive properties. The central role of MC in the control of innate and adaptive immunity endows them with the ability to tune the nature of host responses to cancer and ultimately influence the outcome of disease and fate of the cancer patient.

Increased numbers of gastric-infiltrating mast cells and regulatory T cells are associated with tumor stage in gastric adenocarcinoma patients

“…The transcription factor Foxp3 is a unique marker for Tregs and is indispensable for their development (8,9) Mast cells (MCs) are a group of long-lived heterogeneous cells originating from the bone marrow. They were recognized by their modulating activities in inflammation and angiogenesis until recent investigations revealed their roles in shaping adaptive immune responses (10). MCs have been found to accumulate in the tumor microenvironment through the SCF/c-kit signaling pathway, leading to the aggravation of inflammation and immunosuppression in the tumor microenvironment (11).…”

“…This interaction of MCs with Tregs dictates the intensity of tumor-associated inflammation and thus either promotes or inhibits tumor growth (10).…”

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

“…They support angiogenesis by expression of proangiogenic factors and by inhibition of ECM remodeling the MCs support tumor spread and metastasis. Tumor-associated mast cells are also regarded as potential therapeutic targets [124][125][126][127][128] and prognostic factor [129][130][131].…”

“…Activated MC located in the TME release angiogenic and tumor growth stimulating factors [124,125,381]. Recent findings indicate that tumor-associated mast cells might represent valuable targets for therapeutic interventions, most notably to kinase inhibitors as c-Kit [128,382].…”

Adaptive and Innate Immunity, Non Clonal Players in Colorectal Cancer Progression

“…MCs have been reported to mobilize T cells and antigen-presenting dendritic cells. They modulate Treg-induced tolerance, shifting the local balance of immune surveillance toward pro-inflammatory Treg activation and cancer progression 29 . In light of these evidences, modulating mast cell recruitment, viability, activity, or mediator release patterns could also have important implication in cancer therapy strategies.…”