Tumor‐infiltrating tryptase⁺ mast cells predict unfavorable clinical outcome in solid tumors

Abstract

The prognostic role of tumor-infiltrating tryptase mast cells in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 28 published studies with 4224 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating tryptase mast cells in human solid tumors. We found that tryptase mast cell infiltration significantly decreased overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, tryptase mast cell infiltration was significantly associated with worse OS in non-small cell lung cancer, hepatocellular carcinoma and 5-year survival in colorectal cancer. And these cells were inversely associated with DFS in hepatocellular and colorectal cancer. In addition, high density of intratumoral tryptase mast cells significantly correlated with lymph node metastasis of solid tumor. In conclusion, Tryptase mast cell infiltration leads to an unfavorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances and targeting it may have a potential for effective treatment.

Role of Mast Cells in Shaping the Tumor Microenvironment

“…factors [66]. Tryptase may activate the plasminogen activator and induce the release of VEGF and FGF-2 from their extracellular matrix-bound state [37]. Maniga et al reported the accumulation of MCs in tumors of breast cancer and that MC-derived tryptase is capable of initiating fibroblast differentiation and promoting stromal remodeling [17].…”

Role of Mast Cells in the Control of Aldosterone Secretion

“…Especially, a growing body of evidence indicates that mast cells are implicated in tumor development [68][69][70][71][72][73]. Indeed, these cells are known to favor immunologic tolerance and secrete both growth and angiogenic factors which enhance tumor expansion [74][75][76]. Notably, a positive effect of mast cells has been observed on growth of endocrine neoplasias, including neuroendocrine tumors of thyroid, pancreas, and adrenal (pheochromocytomas) [77][78][79].…”

Role of the tumor microenvironment in pancreatic cancer

“…Furthermore, recent studies have shown that mast cells also affect tumor growth by enhancing angiogenesis, cancer‐cell proliferation and invasion . Mast‐cell infiltration of tumors predicts poor long‐term outcomes for colorectal cancer, hepatocellular carcinoma, colorectal cancer liver metastasis, and pancreatic cancer patients . Kato et al showed that semaphorin‐4D (Sema4D), a membrane‐bound or secreted protein involved in the regulation of antitumor immunity, was demonstrated in TILs in pancreatic cancer tissue.…”