The implications of the TNFα‐TNFR2 immune checkpoint signaling pathway in cancer treatment: From immunoregulation to angiogenesis

Abstract Despite the tremendous advances that have been made in biomedical research, cancer remains one of the leading causes of death worldwide. Several therapeutic approaches have been suggested and applied to treat cancer with impressive results. Immunotherapy based on targeting immune checkpoint signaling pathways proved to be one of the most efficient. In this review article, we will focus on the recently discovered TNFα‐TNFR2 signaling pathway, which controls the immunological and pro‐angiogenic properties of many immunoregulatory and pro‐angiogenic cells such as endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), and regulatory T cells (Tregs). Due to their biological properties, these cells can play a major role in cancer progression and metastasis. Therefore, we will discuss the advantages and disadvantages of an anti‐TNFR2 treatment that could carry two faces under one hood. It interrupts the immunosuppressive and pro‐angiogenic behaviors of the above‐mentioned cells and interferes with tumor growth and survival.