Association of resting mast cell infiltration in the sarcoma microenvironment with overall survival.

Abstract

e14564 Background: Sarcoma remains a challenging solid cancer to treat in the modern era. The role of mast cells in the tumor microenvironment continues to evolve. In the resting state, mast cells function as reservoirs for histamines and cytokines. In the activated state, mast cells degranulate upon encountering pathogens, initiating an immune response. In breast cancer, mast cell presence is associated with a better prognosis in hormone receptor-positive tumors, whereas hepatocellular carcinoma shows the opposite trend. Therapeutic strategies aimed at controlling the tumor microenvironment may also play a role in early detection and prevention of tumor progression. We aim to further understand the role of mast cells in sarcomas. Methods: mRNA sequencing data for 235 sarcoma patients were obtained from The Cancer Genome Atlas (TCGA) and analyzed using CIBERSORT, a Stanford-developed application that quantifies immune cell composition within a tumor sample. Each patient sample was broken down into percentages of various immune cells, including B-cells naïve, B-cells memory, plasma cells, CD8 T-cells, CD4 T-cells naïve, CD4 T-cells memory resting, CD4 T-cells memory activated, T-cells follicular helper, T-cells regulatory Tregs, T-cells gamma delta, natural killer resting cells, natural killer activated cells, monocytes, macrophages (M0, M1, M2), resting dendritic cells, activated dendritic cells, resting mast cells, activated mast cells, eosinophils, and neutrophils. Once the immune cell fractions were obtained, a statistical tool named Radiant by Shiny was used to perform a linear regression to evaluate the relationship between overall survival and the different immune cells. Results: Resting mast cells were independently prognostic of overall survival in multivariable analysis (p = 0.005). The correlation coefficient was +104, indicating a positive association between the number of resting mast cells and overall survival. Conclusions: Patients with a higher number of resting mast cells in their sarcoma microenvironment had longer overall survival. Unlike activated mast cells, which promote inflammation and tumor progression, resting mast cells help maintain immune balance within the tumor microenvironment, potentially leading to a better immune response. One hypothesis is that resting mast cells promote normal vascular function, whereas activated mast cells contribute to pathological angiogenesis. Activated mast cells secrete factors such as histamine and VEGF, which can drive tumor progression, whereas resting mast cells have a secretory profile that is less conducive to cancer spread. Additionally, resting mast cells may remodel the extracellular matrix in a manner that makes it more difficult for cancer to metastasize. These findings position mast cells as potential prognostic tools and therapeutic targets in the world of cancer treatment.