Local and Traditional Medicine in Regulation of the Cancer Immune Suppression Microenvironment, Volume II

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Background

This Research Topic is part of a series. See also Volume I: Local and Traditional Medicine in Regulation of the Cancer Immune Suppression Microenvironment.

According to global cancer statistics, there will be an estimated 18.1 million new cancer cases and 9.6 million cancer deaths in 2018. The tumor microenvironment, which is characterized by tumor immune imbalance, plays a major role in cancer initiation and development. The recruitment of M2 macrophages, regulatory T cells (Tregs) and myeloid-derived suppressor cells participates in the establishment of immune suppression, resulting in the induction of cancer recurrence and metastasis. Dysregulation of immune checkpoint mechanisms further aggravate the escape of cancer cells from therapeutic strategies. Currently, targeting the immune suppression signaling has become a powerful tool for cancer treatment and has gained greater attention worldwide. One of the world-renowned examples of this targeting the PD-1/PD-L1 signaling, which was awarded the Nobel Prize in Physiology and Medicine in 2018. Meanwhile, CAR-T therapies have also demonstrated to provide more precise opportunities to eliminate cancer cells by activating the immune recognition and targeting machinery. However, only around 20% of cancer patients are responsive to immunotherapy, where mixed responses can limit the therapeutic efficacy that results in local recurrence or distant metastasis. Meanwhile, systemic adverse effects such as cytokine storms greatly threaten patients’ lives. All of these may be attributed to the singularity of therapeutic targets, although further investigation is needed.

Local and traditional medicines, which normally contain multiple ingredients that can simultaneously act on multiple targets, has long been tested for cancer adjuvant prevention and treatment due to its systematic regulation on immune function. Multiple studies have demonstrated that conventional formulas could inhibit cancer drug resistance or metastasis via regulating T cell phenotype, macrophage polarization, chemokine expression and immune checkpoints. Meta-analyses of clinical trials have also demonstrated that traditional medical practice could improve cancer patients’ survival period and life quality, accompanied by normalization of tumor immune microenvironment. Meanwhile, a number of traditional Chinese medicine formulas have been commercialized and prescribed to cancer patients with positive clinical efficacy, such as Huaier granule, PHY906 and Huachansu, which shows great effects on tumor microenvironment modulation including macrophage inhibition, T cell differentiation and cytokine secretion. It is interesting and promising to explore the underlying effects and molecular mechanisms of local and traditional medicines in modulating the cancer immune microenvironment.

Nevertheless, the multi-target and multi-ingredient properties of formulas have always been considered to be the biggest challenge for the underlying mechanism exploration. Development of novel techniques or models for evaluating the holistic regulation effects of local and traditional medicines on tumor immune microenvironment has attracted increasing attention worldwide. In the past decade, multiple omics technologies, including genomics, transcriptomic, proteomics, metabolomics and serum pharmacokinetics, have been developed for high-throughput screening and identification of targets involved in complex formulas. Network pharmacology is emerging as one approach to integrate chemical-target interaction from a molecular to a system level, provided that it is linked to experimental pharmacology. Based on the results of omics and systematic analysis, it is becoming easier to develop testable working hypothesis on effects of traditional medicine in regulating the immune response. The immune modulatory effects of local and traditional medicines using cell and animal models is an essential experimental step in order to test such hypotheses (confirming or reputing them). It is expected that the combined application of these technologies will aid further in identifying the targets linking traditional medicine and immune cells. Meanwhile, we also expect to see novel techniques or models to reveal the immune regulation targets of traditional medicine.

By opening up this Research Topic once more, we aim to explore the immune regulation effects and the underlying molecular mechanisms of local and traditional medicines as adjuvants in cancer microenvironment modulation. We encourage Original Research, Review and Perspective articles on the following topics:

- Effects & molecular mechanisms exploration of local and traditional medicines for inhibiting cancer immune suppression microenvironment.

- Omics-based study of local and traditional medicines for cancer immune regulation.

- Network pharmacology analysis & in combination with experimental assessments of the hypotheses generated for specific local and traditional medicines for cancer immune regulation (please note, study using exclusively a network pharmacology are outside of our scope).

- Development of novel models for local and traditional medicines research in cancer immune regulation.

- Clinical studies of local and traditional medicines in regulating tumor immune function. However, please note primary clinical trials will not be accepted for review.

- Reviews or Commentaries of current advancements and limitations of local and traditional medicines for cancer immune regulation.

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All the manuscripts submitted to the collection will need to fully comply with the Four Pillars of Best Practice in Ethnopharmacology (you can freely download the full version here).

Keywords: Traditional Chinese Medicine, immune suppression, tumor microenvironment, Omics, network pharmacology

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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