Antitumor Immunity Is Controlled by Tetraspanin Proteins

Abstract

Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME). In particular, environmental signals (for instance, soluble factors or cell-cell contact) transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9) are widely and broadly expressed, others (CD53, CD37, Tssc6) have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed.

Keywords: adaptive immunity; antitumor immunity; innate immunity; tetraspanins; tumor microenvironment.

Figure 1

Tetraspanins on immune cells in the tumor microenvironment (TME). The TME is comprised of several different cells, including tumor cells and different immune infiltrating cells. Immune cells in the TME produce different soluble factors, including cytokines or antibodies. Each immune cell subset contains its own distinct tetraspanin web composed of tetraspanins that can have either stimulating or inhibitory functions (see Table 1). We hypothesize that immune cells alter the composition of the tetraspanin web when they migrate from the lymph node to the tumor caused by the immunesuppressive environment of tumors. Abbreviations: DC, dendritic cell; MDSC, myeloid-derived suppressor cell.