About this Research Topic

Background

Cancer cells have the ability to evade immune surveillance and resist the anti-tumor immune mechanisms deployed by innate and adaptive immune cells. This is due to the complex interactions between tumor cells and their microenvironment, known as the tumor microenvironment (TME). As a result, immune checkpoint inhibitors (ICIs) have emerged as a prominent form of immunotherapy, targeting immune checkpoints on both cancer and non-cancer cells in the TME. However, ICIs have only shown benefits for a small fraction of patients in clinical trials and real-world clinical practice. One of the main reasons for this is the extensive reshaping of the TME by the interplay and crosstalk among different cell subsets within the TME, which can lead to poor infiltration or inactivation of immune cells.

Recent studies, particularly with the advancements in single-cell technologies, have highlighted the complex and multidimensional interactions among various cell subsets within the tumor immune microenvironment (TME), coupled with longitudinal temporal evolution, which pose significant challenges for anti-tumor immune therapy. For example, tumor-associated macrophages (TAMs) have demonstrated mixed polarization phenotypes, including M1/M2 hybrid macrophages, LYVE1+ macrophages, SPP1+ macrophages, among others, in addition to the previously known M1 and M2 types. Similarly, tumor-associated fibroblasts (CAFs) have been found to exhibit subtypes such as inflammatory CAFs (iCAFs), myofibroblasts (myoCAFs), antigen-presenting CAFs (APC CAFs), etc. Therefore, refining cell subsets (subtypes) and implementing corresponding personalized treatment strategies may be a crucial approach to enhance the effectiveness of immune therapy. Combination therapy (e.g., immunotherapy with chemotherapy, radiation therapy, and targeted therapy) is an ongoing research direction in recent years; Acting against cytokines and other soluble immune modulators, viruses, innate immune modifiers, and cancer vaccines are also valuable therapeutic avenues; the combination of nanotechnology and immunotherapy (nano-immunotherapy) has been extensively studied in recent years.

The primary objective of this Research Topic is to examine the interactions among different cellular subpopulations (subtypes) within the TME, such as stromal cells, immune cells, and tumor cells, and their impact on immunotherapy. The goal of implementing combination therapy is to improve the immunosuppressive state of the TME. We welcome submissions of original research, reviews, mini-reviews, and clinical trials covering a range of subtopics, including but not limited to the following:
- Mechanisms of interaction among different cellular subpopulations (subtypes) in the TME.
- State-of-the-art methods for quantitative analysis of cellular subpopulations (subtypes) in the TME.
- Combination therapy strategies aimed at improving the prognosis of immune checkpoint inhibitors (ICIs) in the treatment of TME.
- Utilization of interdisciplinary techniques to enhance the effectiveness of immunotherapy.

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.

Keywords: Cell subtypes, Adaptive Immune Cells, Tumor Microenvironment, Subpopulations, immune checkpoint inhibitors

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.

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