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.

Molecular mechanisms of dendritic cell migration in immunity and cancer

“…Tetraspanins control several aspects of anti-tumour immunity [164], but their role in DC migration from the tumour to the lymph nodes and vice versa has not been extensively addressed. One study reported increased tumour growth in Cd37 knock-out mice [133].…”

“…This was caused by an impaired T cell-driven anti-tumour immune response due to migration failure of CD37-deficient DCs. Further research on the role of tetraspanins in controlling protein expression and DC signalling may enable the discovery of therapeutic strategies targeting tetraspanins to promote DC migration [164]. In conclusion, studies modulating DC migration in cancer are necessary to determine if this strategy, potentially in combination with current therapies, will improve anti-cancer immunity.…”

Identification of key genes for guiding chemotherapeutic management in ovarian cancer using translational bioinformatics

“…CD53 promotes B cell receptor-dependent protein kinase C signalling (46), and increases tumour growth in Cd53 -/mice (47). Patients with low CD53 expression levels were found to have a poor prognosis.…”

Exosome: A New Player in Translational Nanomedicine

“…These protein superfamilies, together with a wide variety of transmembrane and cytosolic proteins, mediate the organization of tetraspanin-enriched microdomains (TEMS) in the plasma membrane and the biogenesis of exosomes [42,43]. Tetraspanins CD9, CD63, CD81, CD82 and CD151 are widely distributed among the different cell types, while others, such as Tssc6 CD37 and CD53, are restricted to specific tissues [44]. Exosome release by dendritic cells generated from CD9 knockout mice has been demonstrated to be lower than that from wild-type [45].…”