The tumor microenvironment (TME) consists of extracellular matrix proteins, immune cells, vascular cells, lymphatics and fibroblasts. Under normal physiological conditions, tissue homeostasis protects against tumor development. However, under pathological conditions, interplay between the tumor and its microenvironment can promote tumor initiation, growth and metastasis. Immune cells within the TME have an important role in the formation, growth and metastasis of tumors, and in the responsiveness of these tumors to immunotherapy. Recent breakthroughs in the field of cancer immunotherapy have further highlighted the potential of targeting TME elements, including these immune cells, to improve the efficacy of cancer prognostics and immunotherapy. CD38 and CD157 are glycoproteins that contribute to the tumorigenic properties of the TME. For example, in the hypoxic TME, the enzymatic functions of CD38 result in an immunosuppressive environment. This leads to increased immune resistance in tumor cells and allows faster growth and proliferation rates. CD157 may also aid the production of an immunosuppressive TME, and confers increased malignancy to tumor cells through the promotion of tumor invasion and metastasis. An improved understanding of CD38 and CD157 in the TME, and how these glycoproteins affect cancer progression, will be useful to develop both cancer prognosis and treatment methods. This review aims to discuss the roles of CD38 and CD157 in the TME and cancer immunotherapy of a range of solid tumor types.Cells 2020, 9, 26 2 of 18 inhibit tumor growth and development [5,9]. Surface glycoproteins expressed by immune infiltrates can be used as biomarkers for classification of the immune cells. These glycoproteins also influence the pro-or anti-tumor activity of immune cells. Thus, the presence and functions of glycoproteins on the surface of tumor immune infiltrates are currently subjected to intense study.CD38 and CD157 are two such glycoproteins of particular interest in the field of immunotherapy. They are coded by contiguous gene sequences found on human chromosome 4, and are thought to originate from gene duplication. These gene sequences share similarities in terms of length and the organization of introns and exons, and the resultant proteins share similar functions [10]. CD38 and CD157 function as both receptors and ectoenzymes, and belong to the same family of nicotinamide adenine dinucleotide (NAD+) converting enzymes.CD38 is involved in lymphocyte activation, proliferation and adhesion. Initially thought to be expressed only by thymic lymphocytes, it has since been found to be ubiquitously expressed by immune cells, including B lymphocytes, natural killer cells and monocytes; and its expression varies across both lymphoid and non-lymphoid tissues [10,11]. In contrast, CD157 is mainly expressed by cells derived from the myeloid lineage, and in particular by neutrophils and monocytes. CD157 is also expressed by a wide range of non-lymphoid tissues, including vascular endothelium, kidney collecting tubu...
