About this Research Topic
The tumor microenvironment (TME) consists of various cell types (immunosuppressive cells, fibroblasts, neurons, stromal cells, endothelial cells, etc.), signaling molecules (cytokines, growth factors, hormones, extracellular matrix, etc.) and surrounding blood vessels. Increasing evidences indicate that the interplay between these components is responsible for tumor initiation, progression, and metastasis. In addition, targeting the TME, especially immunosuppressive cells such as myeloid-derived suppressive cells (MDSCs), Regulatory T cells (Treg) and tumor-associated macrophage (TAM), is particularly efficient in the treatment of several malignancies. Furthermore, it has been showed that metabolic perturbations not only of tumor cells, but also of TME components, including genetic and epigenetic dysfunctions, are considered as an hallmark of cancer. Despite the rapid progress of the TME field in the past decades and the translation of some of these findings into preclinical trials, still a lot remains to be investigated about the nature and function of the TME components.
Immuno-metabolism and metabolic reprogramming of different immunosuppressive cells have been considered as a key to maintain tumor growth, metastasis, drug resistance and motility. However, much more remains to be understood regarding the contribution of some immunosuppressive cells, such as MDSCs, Treg and TAM, and their immune-metabolic characteristics: (i)What are the metabolic and functional differences of immunosuppressive cells from normal cells in TME? (ii) What signals do these cells transmit or receive from the TME? (iii) How does immune-metabolism of immunosuppressive cells in TME change after novel immunotherapy, such as mAbs for immune checkpoints or CAR-T? All these mechanisms might drive immunotherapeutic resistance and, therefore, need to be clarified. Additionally, the interplay between cancer and immunosuppressive cells still needs to be characterized in terms of oncogenic, metabolic, and epigenetic signaling, as it represents a source of potential novel therapeutic strategies or drugs regulating the anti-tumor response. In the light of these observations, manipulating the TME’s metabolic milieu might enhance the benefits of clinical immunotherapy.
This Research Topic aims to highlight the ongoing advances and challenges in the field of tumor microenvironment biology and manipulation, and to provide insights into a variety of ongoing questions in its immune-metabolism and epigenetic regulation. We welcome Original Research articles and Mini-reviews covering, but not limited to, the following themes:
• Metabolic heterogeneity of key immunosuppressive cells within TME
• Targeting the crosstalk between stromal cells and immunosuppressive cells within TME
• Epigenetic and transcriptional regulation of immune milieu of the TME: from the bench to the clinic
• Challenges in novel immune checkpoints therapeutics targeting the TME
• Manipulating TME by adoptive cell transfer of CAR T cells.
• Novel drugs for TME manipulation
• Novel mechanisms of resistance to immunotherapy that arise in TME
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.