Abstract

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.

Highlights

  • Cancer immunotherapy has been advancing exponentially [1,2]

  • It is clear that the dual enzymatic and receptorial functions of CD38 mean that this glycoprotein affects the immune response in a number of ways, and these must be fully characterized to improve the accuracy of cancer prognosis and efficacy of treatment

  • The tumor microenvironment (TME) consists of extracellular matrix proteins, immune cells, vascular cells, lymphatics and fibroblasts, and is of great importance to a cancer’s responsiveness to immunotherapy

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Summary

Background

Identification of targets in the biological pathways of tumor cells successfully led to development of monoclonal antibody and tyrosine kinase inhibitor drugs, actively used in cancer treatment. Immune cells present within the TME may either promote or inhibit tumor growth and development [5,9]. Of tumor immune infiltrates currently can be used as functions biomarkersoffor classificationon of the These glycoproteins are influence the subjected to intense study. The organization ofgene introns and exons, and the resultant proteins shareand similar originate from gene These sequences share similarities in terms of length the functions [10]. CD38 is involved in lymphocyte activation, proliferation and Initially thought by to immune cells,only including. In different cancers is consolidated from relevant data and evidence available in existing literature

The Role of CD38 in the TME
The Role of CD157 in the TME
CD38 and CD157 as Targets for Cancer Immunotherapy
CD157 show summary of the known functions ofprognostic
Functions of CD38
CD38 in Hepatocellular Carcinoma
CD38 in the Solid Tumor Microenvironment
CD38 in Non-Small Cell Lung Cancer
CD38 in Melanoma
CD38 in Pancreatic Ductal Adenocarcinoma
CD38 in Glioma
CD38 in Breast Cancer
CD157 in Ovarian Cancer
CD157 in Pleural Mesothelioma
Potential Functions of CD157 in Other Types of Tumor
Findings
Conclusions
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