Frenemies in the Microenvironment: Harnessing Mast Cells for Cancer Immunotherapy

Abstract

Tumor development, progression, and resistance to therapies are influenced by the interactions between tumor cells and the surrounding microenvironment, comprising fibroblasts, immune cells, and extracellular matrix proteins. In this context, mast cells (MCs) have recently emerged as important players. Yet, their role is still controversial, as MCs can exert pro- or anti-tumor functions in different tumor types depending on their location within or around the tumor mass and their interaction with other components of the tumor microenvironment. In this review, we describe the main aspects of MC biology and the different contribution of MCs in promoting or inhibiting cancer growth. We then discuss possible therapeutic strategies aimed at targeting MCs for cancer immunotherapy, which include: (1) targeting c-Kit signaling; (2) stabilizing MC degranulation; (3) triggering activating/inhibiting receptors; (4) modulating MC recruitment; (5) harnessing MC mediators; (6) adoptive transferring of MCs. Such strategies should aim to either restrain or sustain MC activity according to specific contexts. Further investigation would allow us to better dissect the multifaceted roles of MCs in cancer and tailor novel approaches for an “MC-guided” personalized medicine to be used in combination with conventional anti-cancer therapies.

Impaired Proliferation of CD8+ T Cells Stimulated with Monocyte‐Derived Dendritic Cells Previously Matured with Thapsigargin‐Stimulated LAD2 Human Mast Cells

“…Mast cells (MCs) are long-lived terminally differentiated tissue or mucosa-resident cells [ 1 ]. Although these cells are largely associated with asthma, allergy, atopy, and anaphylaxis [ 2 , 3 ], they also play a significant role in cancer development, autoimmune diseases, and regulation of other components of the immune system under physiologic or pathologic conditions [ 4 , 5 , 6 ]. The regulation can be mediated either via direct contact with other immune cells [ 7 , 8 ] or through biologically active products released after their stimulation [ 9 , 10 ].…”