Lewis Lung Carcinoma (LLC) alters the phenotype of murine lung mast cells resulting in a phenotype consistent with myeloid‐derived suppressor cells (MDSCs)

Abstract

MDSCs are among the most potent immune suppressive phenotypes found in the tumor microenvironment. Because they share so many characteristics with myeloid progenitors, MDSCs are thought to arise as a product of tumor‐associated hematopoiesis. However, a clear MDSC progenitor has yet to be identified. We used flow cytometry to demonstrate a significant increase in CD11b+ infiltrate in a murine model of LLC as compared to normal lung tissue. A large portion of this infiltrate also expresses the granulocyte/myeloid marker Gr‐1. Interestingly, CD11b+/Gr‐1+ cells in normal lung tissue also express the high affinity IgE receptor FcεR1α, which is indicative of mast cells. However, this FcεR1α expression is lost on these cells in LLC‐bearing animals in a tumor burden‐dependant manner. Additionally, conventional methylene blue stains show highly granulated mast cells in normal lung tissue while showing a complete lack of granulated cells in LLC‐bearing lung tissue. We also immunomagnetically isolated Gr‐1+ mast cells out of normal lung tissue and incubated them in‐vitro with LLC‐conditioned media while monitoring their FcεR1α expression, granularity, and morphology in an attempt to reproduce the phenotypic changes seen in‐vivo. Our data suggests that in LLC, MDSCs may originate from fully differentiated mast cells rather than from myeloid precursors.Supported by the Dept of Veteran's Affairs & NIH