Tumor-associated Mast Cells Research Articles

Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP

AbstractGene expression profiling and immunohistochemical studies have demonstrated that nonmalignant tumor infiltrating inflammatory cells contribute to clinical outcome in patients with follicular lymphoma (FL). Particularly, tumor-associated macrophage (TAM) content correlates with longer survival rates after immunochemotherapy. Here we investigated the prognostic importance of tumor-associated mast cells (MCs) and their relation to TAMs in patients with FL treated with a combination of rituximab (R) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Of the 98 patients, 70 received R-CHOP at diagnosis and 28 at relapse. According to Kaplan-Meier estimates, the patients with high MC content had a worse 4-year progression-free survival (PFS) than the ones with low MC content after R-CHOP therapy (34% vs 74%, P = .002). The adverse prognostic value of MCs was seen both for the patients treated at diagnosis and at relapse, whereas no such impact on PFS was observed for the control patients treated with chemotherapy only (P = .4). When the TAM-related PFS was analyzed separately in patients with high and low MC contents, the positive prognostic effect of TAM was seen only in patients with few MCs. Taken together, the data demonstrate that a high MC score is associated with unfavorable prognosis and it eliminates the positive prognostic value of TAMs in patients with FL treated with immunochemotherapy.

The Prognostic Significance of Mast Cell Count in Soft Tissue Sarcomas

Mast cells (MC) are known to play an important role in IgE-dependent allergic reaction, host defense against parasite infestation, local hemostasis, inflammation, and angiogenesis. The significance of MC in tumor surveillance has been studied with conflicting results. The presence of MC in tumor has been described as evidence of a host immunologic antitumor response, and a high count of tumor-associated MC has been considered as a favorable prognostic factor in sarcomas. In other studies, MC have been shown to have an adverse role in neoplastic proliferation. In this study, tumor-associated MC were histologically quantitated in 75 soft tissue sarcomas. We found that soft tissue sarcomas with a higher MC count (n=or>six) were associated with significant better survival and relatively low incidence of metastasis in contrast to those with a lower count (n<six). There was no correlation between MC count and the histologic type, grade, or size of the sarcomas. Although the role of mast cells in tumor surveillance is still under investigation, quantitive assessment of tumorassociated MC on routine histologic sections could be used as an additional prognostic factor in soft tissue sarcomas.

Human mast cell tryptase activates single-chain urinary-type plasminogen activator (pro-urokinase)

Human lung mast cell tryptase is a trypsin-like serine proteinase that is stored in mast cell granules and released by activated mast cells. Here we report that mast cell tryptase is a potent activator of single-chain urinary-type plasminogen activator (scu-PA, or prourokinase), the zymogen form of urinary-type plasminogen activator (u-PA). Activation was complete within 75 min using an enzyme:substrate molar ratio of 1:50 and was accompanied by cleavage of scu-PA at Lys158-Ile159, generating active two-chain u-PA. The reaction was dependent on enzyme concentration and obeyed Michaelis-Menten kinetics. Kinetic constants calculated for scu-PA activation by mast cell tryptase are Km = 34 microM, Vmax = 3.6 pmol of u-PA/min, and kcat = 0.08 s-1. These data suggest that tryptase from tumor-associated mast cells may participate in the activation of scu-PA.