This Research Topic is the second volume of the “Community Series in Cell Network in Antitumor Immunity of Pediatric and Adult Solid Tumors”. Please see the first volume here
The importance of the immune system in sustaining or limiting tumor growth, with its immunosuppressive or immune-stimulatory properties is now well established, and has spawned a new era for cancer treatment. Successful anti-tumor immune response requires the contribution of cells of innate and adaptive immunity that should work in concert to trigger tumor-cell killing. Specifically, key steps include the uptake of tumor antigen by dendritic cells (DCs) within the tumor, trafficking activated DCs to tumor-draining lymph nodes, priming T cells against tumor antigens, infiltration of tumor-specific T cells into cancer tissues, and their activation for tumor cell lysis. In this context, all the other immune cell types, including natural killer (NK) cells, B-cells, macrophages, mast cells, and neutrophils can also infiltrate tumor tissues. Based on their type, density, activation status, and mutual functional relationship, these cells may contribute to the anti-tumor effect. Alternatively, they can induce immune tolerance, leading to tumor progression and spread.
In addition to immune populations, the tumor microenvironment (TME) is composed of a variety of different cellular and non-cellular components of the extracellular matrix, capable of establishing complex signaling networks that can promote or weaken anti-tumor immunity. Indeed, most of the cell types interact with each other within the TME via direct cell-cell contact and paracrine factors. Little is known about these multiple interactions, but shedding light on this cellular chatter may be key to figuring out therapeutic strategies that can prevent immune evasion and stimulate long-lasting anticancer immune responses.
In this regard, immunotherapy has led to successful clinical trials for various adult tumor types, with many investigations currently ongoing for pediatric tumors. Administration of single checkpoint inhibitors has been unsuccessful in most cases, whereas the combination of therapeutic strategies that can inhibit immunosuppression and activate tumor-specific T cells is currently holding out great hope. There is considerable interest in identifying suitable immunomodulatory therapeutic agents for each malignancy. A promising immunotherapeutic tool for T-cell resistant tumors lies in NK cells. However, despite these various therapeutic approaches, many cancer patients still do not respond or relapse.
This Research Topic will focus on cellular communication within the TME during cancer initiation, progression, and response to therapy, with emphasis on the effect cancer cells have on the immune system function and on the intersection of innate and adaptive immunity in the TME. It will also look at the influence of the other cellular components of the TME on anti-tumor immune response.
We welcome the submissions of Original Research Articles, Reviews, Mini Reviews, Methods, and Perspectives addressing cell-cell interactions as critical determinants to activation or exhaustion of immune response within the TME of pediatric and adult solid neoplasms. This can include, but is not limited to, the following sub-topics:
• Regulation of innate and adaptive immunity by the TME.
• Molecular mechanisms underlying interactions between immune cells and tumor cells/blood cells/adipocytes/pericytes/stromal cells.
• Myeloid/lymphoid communication with TME during cancer progression.
• Optimization of existing immunomodulatory drugs that, targeting TME, restore or boost the adaptive immune response against cancer cells.
• Identification of new therapies that, by interfering with the cellular crosstalk, reprogram a dysfunctional microenvironment in favor of effective anti-tumor immunity.
• Understanding how interactions between cancer cells, immune cells, and the other components of the TME affect therapy-based anti-checkpoint inhibitors.
• Exploration of novel biomarkers and therapeutic targets related to cell-cell interaction within TME.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.