Tumor Immune Microenvironment Topographies for Prediction and Evaluation: Unlock the Mystery of the Therapeutic Effects and Adverse Events of Tumor Immunotherapy

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Background

The tumor microenvironment (TME) is a complex integrated system composed of tumor cells, stromal cells, and tumor-infiltrating inflammatory cells (TIICs). Tumor cells undergo Warburg Effect to adapt TIICs, and there exists competition between anti-tumor immunity and immune cell-mediated tumor promotion, metastasis, drug resistance, and immune escape. Accumulating evidence indicates that the intricate crosstalk between them crucially orchestrates the fate of a tumor. Nowadays, immunotherapies such as immune checkpoint blockade or genetically engineered T cells have achieved unprecedented success. However, a large fraction of patients fail to respond, and the mechanisms of primary or acquired drug resistance are still not sufficiently understood. Meanwhile, immune-related adverse events frequently threaten the lives of patients. The growing need presses us to develop new medicines as well as novel detection and treatment strategies targeting the immune system so that there can be more effective outcomes while ensuring patient safety. The detailed mechanisms by which TIICs act on tumors and the role of tumor cells in shaping the tumor immune microenvironment remain elusive. The challenge is initiating a strong anti-tumor immune response in a suitable TME by breaking through immunosuppression and immune exclusion. Hence, reshaping the immune TME could be a potential method. Moreover, insight into the individual characteristics of TME could also help in the development of immunotherapy strategies. A better understanding of their interplay is worthy of further exploration, which could affect clinical outcomes in pan-tumor immunotherapy.

Tumor precision immunotherapy is based on the analysis of each patient's genetic basis biomarkers to choose a more appropriate individualized therapeutic regimen. To this end, an in-depth identification of biomarkers for characterization of the TIICs landscape is urgently required for optimizing the benefits of immunotherapy and reducing the relative treatment risks.

This Research Topic aims to highlight projects that focus on extending and deepening our understanding to construct a topographic map of the tumor immune microenvironment. We would like to create a forum with specific factors to predict and evaluate anti-tumor immunotherapies with special consideration for patient safety. We hope that research within this topic will lead to novel immunotherapy strategies and translate predictions into safe and efficacious immunotherapies, leading to new opportunities and benefits for patients. We welcome manuscripts related to, but not limited to, the following subtopics:

• Identifying the novel technologies and prognostic models based on clinical characteristics of patients, immune TME and association between TIICs and tumor cells for the response to immunotherapies with translation potential (multi-omics analyses or biomarkers, bio-imaging techniques, clinical predictive models, or computational methods for prediction):
- Prediction and evaluation methods or biomarkers for the tumor sensitivity and/or the prognosis for patients who have received immunotherapies of novel immunotherapy strategies
- Prediction and evaluation of the risks for patients who might be damaged or even experience life-threatening immunotherapy-related adverse events

• Delineating the characteristics and exploring the mechanism of the tumor-associated immune landscape at the single-cell level (signaling pathways, cytokines, or exosomes):
- The genetic and epigenetic modifications focusing on mutation-associated neoantigens and tumor immune microenvironment, including Treg, TAMs, or MDSCs targeting agents and immune suppressive pathways inhibitors
- The interplay mechanisms between TIICs and tumor cells, and effects on improving the efficacy and avoiding the drug resistance of immunotherapies
- The utilization of distinct, alternative, and enhanced metabolic pathways in pre-metastatic niches and tumor immune microenvironment

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: Tumor Immune Microenvironment, Topographies, Prediction and Evaluation, Tumor Immunotherapy

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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