Steering Mast Cells or Their Mediators as a Prospective Novel Therapeutic Approach for the Treatment of Hematological Malignancies

Abstract

Tumor cells require signaling and close interaction with their microenvironment for their survival and proliferation. In the recent years, Mast cells have earned a greater importance for their presence and role in cancers. It is known that mast cells are attracted towards tumor microenvironment by secreted soluble chemotactic factors. Mast cells seem to exert a pro-tumorigenic role in hematological malignancies with a few exceptions where they showed anti-cancerous role. This dual role of mast cells in tumor growth and survival may be dependent on the intrinsic characteristics of the particular tumor, differences in tumor microenvironment according to tumor type, and the interactions and heterogeneity of mediators released by mast cells in the tumor microenvironment. In many studies, Mast cells and their mediators have been shown to affect tumor survival and growth, prognosis, inflammation, tumor vascularization and angiogenesis. Modulating mast cell accumulation, viability, activity and mediator release patterns may thus be important in controlling these malignancies. In this review, we emphasize on the role of mast cells in lymphoid malignancies and discuss strategies for targeting and steering mast cells or their mediators as a potential therapeutic approach for the treatment of these malignancies.

A case of high‐risk AML in a patient with advanced systemic mastocytosis

“…24 As a consequence, the residual MC infiltrates potentially create a favorable substrate for further progression or the recurrence of the associated hematologic neoplasms. 25 Within a short time the patient became refractory to the triplet (DEC-VEN-MIDO) and was immediately hospitalized in order to undergo salvage therapy with HAM regimen (for R/R-AML) associated with cladribine (both for AdvSM and R/R-AML) as a bridge to transplant. 13 Relapsed/refractory (R/R) AML remains an impervious hematologic challenge with generally poor outcomes and despite the existence of a wide armamentarium of second-line regimens, none of them is significantly beneficial compared to the others.…”

“…Most importantly, MCs release numerous factors (histamine, heparin, tryptase, cytokines) in the microenvironment, thus enhancing tumor‐associated angiogenesis 24 . As a consequence, the residual MC infiltrates potentially create a favorable substrate for further progression or the recurrence of the associated hematologic neoplasms 25 …”

“… 24 As a consequence, the residual MC infiltrates potentially create a favorable substrate for further progression or the recurrence of the associated hematologic neoplasms. 25 …”

Low Tumor Infiltrating Mast Cell Density Reveals Prognostic Benefit in Cervical Carcinoma

“…There was a potential to suppress neo-vascularization through decreasing MC degranulation and reducing MC numbers, leading to a delay in the tumor growth. 26 It has already proved to be a rational and effective additional therapeutic strategy for tumors negatively affected by MCs. But there are still some limitations that cannot be ignored.…”

“…The number of tumor-infiltrating MCs was related to increased microvessel density in the tumor, enhanced tumor growth and invasion, and poor clinical prognosis. 26,27 MCs release molecules like vascular endothelial growth factor (VEGF), tryptase, fibroblast growth factor (FGF-2), which can initiate tumor angiogenesis, and molecules like matrix metalloproteinases (MMP-9 and MMP-2) which can enable tumor niche remodeling, migration and invasiveness collectively resulting in cancer progression. 24 However, there is still controversy on the density of MC and the prognosis of CC patients.…”