About this Research Topic
The relationship between inflammation and immunosuppression is complex. A key molecule linking these two systems is Tumor Necrosis Factor (TNF) which whilst being a master pro-inflammatory cytokine, with anti-TNF therapy becoming a mainstay treatment for some autoimmune diseases, it also activates regulatory T cells (Tregs), resulting in their expansion, as well as promoting their phenotypic stability, and enhanced immunosuppressive capacity. This effect of TNF is mediated by TNFR2, which is preferentially expressed by immune cells, and specifically abundantly on human and mouse Tregs. Emerging literature further suggests TNFR2 may be expressed on cancer cells, as well as other immunosuppressive cell types that often infiltrate tumors, such as myeloid derived suppressor cells (MDSC), as well as Mesenchymal stem cells (MSCs), promoting cancer survival in the host. This picture is further complicated by the fact that TNF can also interact with TNFR1, another TNF receptor ubiquitously expressed by nearly all type of nucleated cell types. Furthermore, TNFR2, as a membrane receptor, can be secreted and its soluble form, sTNFR2, is capable of neutralizing TNF activity. Despite this complexity, TNFR2 has emerged as a novel target for the treatment of cancer, autoimmune diseases, and GvHD, as well as for potentially enhancing current vaccines and immunomodulators. Additionally, sTNFR2 is emerging as a potential diagnostic soluble factor, its new potential utility is suggested to range broadly from malaria and cancer to mental health.
This Research Topic summarizes the latest knowledge on the central role of TNF-TNFR2 signaling on the biology of multiple cell types, including cancer cells, Tregs and other immunosuppressors, and analyzes its implications in the treatment of cancer or control of harmful inflammatory responses. We aim to bring together contributions from scientists involved in fundamental research community as well as in clinical research for an in-depth discussion, which will point to future directions and relevant translational studies. To this end, we encourage the submission of original research and review articles on the role of TNFR2 expression across multiple immune cell types, and the potential utility such insights will bring to understand the relationship between inflammation and immunosuppression, as well as the development of novel therapeutics, diagnostics, and prognostics.
Keywords: TNFR2, TNF, Tregs, immunotherapy, diagnostics, prognostics, cancer, autoimmune diseases, MSCs, MDSCs, infectious disease, allergy, asthma
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.