A combinatorial αβ T cell receptor expressed by macrophages in the tumor microenvironment

Abstract

Recent evidence indicates the presence of macrophage subpopulations that express the TCRαβ in two major inflammatory diseases, tuberculosis and atherosclerosis. Inflammation is also a well-established attribute of cancer progression and macrophages are one of the major immune cells that infiltrate tumors. Here, we demonstrate that the macrophage-TCRαβ is expressed in the tumor microenvironment of human and murine malignancies. We identify TCRαβ⁺ macrophages in each case of four randomly selected distinct human tumor entities. In human tumor tissues, the TCRαβ expressed by macrophages in the tumor microenvironment is a combinatorial and individual-specific immune receptor. Furthermore, we routinely find TCRαβ⁺ macrophage subpopulations in experimental tumors (TS/A, mammary adenocarcinoma) which we induced both in normal mice and mice deficient in the macrophage receptor stabilin-1. Expression of the combinatorial murine tumor macrophage TCRαβ is individual-specific and independent of stabilin-1. These results demonstrate that TCRαβ expression is a characteristic feature of macrophages in the tumor microenvironment and identify an as yet unrecognized flexible element in the macrophage-based host response to tumors.

Keywords: Macrophages in the tumor microenvironment; TCRαβ; Variable immune receptor.