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The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor- α , and IFN- γ , as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor- β , and tumor necrosis factor- β. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. Whether direct cell-cell interactions are important in modulating MC/DC function is unclear . In this paper, we show that direct contact between MCs and DCs occurs and plays an important role in modulating the immune response. Activation of MCs through FceRI cross-linking triggers the formation of stable cell-cell interactions with immature DCs that are reminiscent of the immunological synapse. Direct cellular contact differentially regulates the secreted cytokine profile, indicating that MC modulation of DC populations is influenced by the nature of their interaction. Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. The transferred material is ultimately processed and presented by DCs and can activate T cells. The physiological outcomes of the MC-DC synapse suggest a new role for intercellular crosstalk in defining the immune response. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Traditional Chinese herbal medicine (CHM) has a long-history for treatment of various human diseases including tumors, infection, autoimmune diseases in Asian countries, especially in China, Japan, Korea and India. CHM was traditionally used as water extracts and many Chinese herbs were considered to be good for health, which can regulate immune system to protect host from diseases. With the progress of technology, the components of CHM were identified and purified, which included polysaccharides, saponins, phenolic compounds, flavonoids and so on. Recently, accumulating evidence indicates that CHM and its components can regulate immune system through targeting dendritic cells (DCs). We hereby reviewed the immunoregulatory effects of CHM on the maturation, cytokine production and function of DCs. This should help to shed light on the potential mechanism of CHM to improve the usage and clinical efficacy of CHM. Materials and methods Literatures about the effects of CHM on DCs were searched in electronic databases such as Pubmed, Google Scholar and Scopus from 2000 to 2014. ‘CHM’, ‘DC’ or ‘immune’ were used as keywords for the searches. We only reviewed literatures published in English. Results Over 600 publications were found about ‘CHM&immune’ and around 120 literatures about ‘CHM&DC’ were selected and reviewed in this paper. All publications are backed by preclinical or clinical evidences both in vitro and in vivo . Some CHM and its components promote the maturation, pro-inflammatory cytokine production and function of DCs and as the adjuvant enhance immune responses against tumor and infection. In contrast, other CHM and its components suppress the activation status of DCs to induce regulatory T cells, inhibit allergic and inflammatory responses, ameliorate autoimmune diseases, and prolong the allograft survival. A large body of evidence shows that CHM and its components regulate the activation status of DCs through TLRs, NF-κB, MAPK signaling pathways. Conclusion This review provides useful information for understanding the mechanism of CHM on the treatment of diseases, which facilitates to improve the efficacy of CHM. Based on the immunoregulatory effects of CHM on DCs, it indicated that some CHM and its components could be use to develop adjuvant to enhance antigen-specific immune responses or tolerogenic adjuvant to generate antigen-specific immune tolerance. [ABSTRACT FROM AUTHOR]

Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most common inflammatory skin disease, affecting an average of 2–4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is the most common primary bone tumor and has a poor prognosis. Therefore, it is important to understand the mechanism of the development of osteosarcoma to overcome therapy resistance. Several mathematical models have been developed to study the initiation and progression of many cancer types. However, there are currently no mathematical models for the progression of osteosarcoma, to the best of our knowledge. In this work, we develop a data-driven mathematical model to analyze the impact of the immune cell interactions on the growth of osteosarcoma tumors that have distinct immune patterns. Our model provides a foundation for investigating the effect of various treatments on the dynamics of key players in the primary tumor, including immune cells and cytokines, and ultimately the whole tumor. As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance of immune cells as estimated from their gene expression profiles. We then analyze the tumor progression and effects of the immune system on cancer growth in each cluster. Cluster 3, which had approximately the same number of naive and M2 macrophages, had the slowest tumor growth, and cluster 2, with the highest population of naive macrophages, had the highest cancer population at the steady states. We also found that the fastest growth of cancer occurred when the anti-tumor immune cells and cytokines, including dendritic cells, helper T cells, cytotoxic cells, and IFN- γ , switched from increasing to decreasing, while the dynamics of regulatory T cells switched from decreasing to increasing. Importantly, the most impactful immune parameters on the number of cancer and total cells were the activation and decay rates of the macrophages and regulatory T cells for all clusters. This work presents the first osteosarcoma progression model, which can be later extended to investigate the effectiveness of various osteosarcoma treatments. [ABSTRACT FROM AUTHOR]