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Several immune and immunocompetent cells, including dendritic cells, macrophages, adipocytes, natural killer cells, T cells, and B cells, are significantly correlated with the complex discipline of oncology. Cytotoxic innate and adaptive immune cells can block tumor proliferation, and others can prevent the immune system from rejecting malignant cells and provide a favorable environment for tumor progression. These cells communicate with the microenvironment through cytokines, a chemical messenger, in an endocrine, paracrine, or autocrine manner. These cytokines play an important role in health and disease, particularly in host immune responses to infection and inflammation. They include chemokines, interleukins (ILs), adipokines, interferons, colony-stimulating factors (CSFs), and tumor necrosis factor (TNF), which are produced by a wide range of cells, including immune cells, such as macrophages, B-cells, T-cells, and mast cells, as well as endothelial cells, fibroblasts, a variety of stromal cells, and some cancer cells. Cytokines play a crucial role in cancer and cancer-related inflammation, with direct and indirect effects on tumor antagonistic or tumor promoting functions. They have been extensively researched as immunostimulatory mediators to promote the generation, migration and recruitment of immune cells that contribute to an effective antitumor immune response or pro-tumor microenvironment. Thus, in many cancers such as breast cancer, cytokines including leptin, IL-1B, IL-6, IL-8, IL-23, IL-17, and IL-10 stimulate while others including IL-2, IL-12, and IFN-γ, inhibit cancer proliferation and/or invasion and enhance the body's anti-tumor defense. Indeed, the multifactorial functions of cytokines in tumorigenesis will advance our understanding of cytokine crosstalk pathways in the tumor microenvironment, such as JAK/STAT, PI3K, AKT, Rac, MAPK, NF-κB, JunB, cFos, and mTOR, which are involved in angiogenesis, cancer proliferation and metastasis. Accordingly, targeting and blocking tumor-promoting cytokines or activating and amplifying tumor-inhibiting cytokines are considered cancer-directed therapies. Here, we focus on the role of the inflammatory cytokine system in pro- and anti-tumor immune responses, discuss cytokine pathways involved in immune responses to cancer and some anti-cancer therapeutic applications. [ABSTRACT FROM AUTHOR]

Tumor metastasis is a major cause of death in cancer patients. It involves not only the intrinsic alterations within tumor cells, but also crosstalk between these cells and components of the tumor microenvironment (TME). Tumorigenesis is a complex and dynamic process, involving the following three main stages: initiation, progression, and metastasis. The transition between these stages depends on the changes within the extracellular matrix (ECM), in which tumor and stromal cells reside. This matrix, under the effect of growth factors, cytokines, and adipokines, can be morphologically altered, degraded, or reorganized. Many cancers evolve to form an immunosuppressive TME locally and create a pre-metastatic niche in other tissue sites. TME and pre-metastatic niches include myofibroblasts, immuno-inflammatory cells (macrophages), adipocytes, blood, and lymphatic vascular networks. Several studies have highlighted the adipocyte-macrophage interaction as a key driver of cancer progression and dissemination. The following two main classes of macrophages are distinguished: M1 (pro-inflammatory/anti-tumor) and M2 (anti-inflammatory/pro-tumor). These cells exhibit distinct microenvironment-dependent phenotypes that can promote or inhibit metastasis. On the other hand, obesity in cancer patients has been linked to a poor prognosis. In this regard, tumor-associated adipocytes modulate TME through the secretion of inflammatory mediators, which modulate and recruit tumor-associated macrophages (TAM). Hereby, this review describes the cellular and molecular mechanisms that link inflammation, obesity, and cancer. It provides a comprehensive overview of adipocytes and macrophages in the ECM as they control cancer initiation, progression, and invasion. In addition, it addresses the mechanisms of tumor anchoring and recruitment for M1, M2, and TAM macrophages, specifically highlighting their origin, classification, polarization, and regulatory networks, as well as their roles in the regulation of angiogenesis, invasion, metastasis, and immunosuppression, specifically highlighting the role of adipocytes in this process.

Purpose: The relationships among circulating tumor cells (CTCs), inflammatory cells, and platelets in patients with renal cell carcinoma (RCC) are not transparent. We evaluated the correlations among CTCs, blood inflammatory cells, and platelets in patients with RCC and their prognostic value for metastasis-free survival.Methods: CTC and typical tumor cell chip data were collected and analyzed by the GEO database. The baseline data, survival data, CTCs data, and blood test results were statistically analyzed.Results: Bioinformatics analysis showed that the function of the differentially expressed genes between CTCs and normal tumor cells mainly involved platelets and immune inflammation. A total of 82 patients whose follow-up time was 3 to 68 months were included in the analysis. Clinical data of the patients confirmed that there is a correlation between platelets and mesenchymal CTCs. Simultaneously, there was a correlation between immune inflammatory cells and platelets. The univariate Cox proportional hazards model indicated that staging, mesenchymal CTCs, and the monocyte-to-neutrophil ratio (MNR) had prognostic value. The multivariate Cox proportional hazards model indicated that staging and the MNR had prognostic value and high accuracy.Conclusions: Bioinformatics analysis showed that CTCs were related to platelets and immune-inflammatory cells. Furthermore, the clinical data confirmed that platelets were correlated with mesenchymal CTCs and immune-inflammatory cells in the blood. By using mesenchymal CTCs, the MNR, or staging respectively, it is possible to predict the risk of postoperative metastasis in RCC patients. As a compound prognostic factor, staging, and the MNR can provide more convenient and accurate condition monitoring. [ABSTRACT FROM AUTHOR]

Simple Summary: The inflammatory adipose microenvironment in obesity plays a crucial role in cancer development and metastases. By focusing on adipocytes and macrophages, as well as the extracellular matrix, the cellular and molecular mechanisms that link inflammation, obesity, and cancer will be addressed by this review. After describing the tumor microenvironment and extracellular matrix, the influence of M1, M2, and tumor-associated macrophages will be explored through their origin, classification, polarization, and regulatory networks, including their potential role in angiogenesis, invasion, metastasis, and immunosuppression, with a specific focus on the roles of adipocytes in this process. Tumor metastasis is a major cause of death in cancer patients. It involves not only the intrinsic alterations within tumor cells, but also crosstalk between these cells and components of the tumor microenvironment (TME). Tumorigenesis is a complex and dynamic process, involving the following three main stages: initiation, progression, and metastasis. The transition between these stages depends on the changes within the extracellular matrix (ECM), in which tumor and stromal cells reside. This matrix, under the effect of growth factors, cytokines, and adipokines, can be morphologically altered, degraded, or reorganized. Many cancers evolve to form an immunosuppressive TME locally and create a pre-metastatic niche in other tissue sites. TME and pre-metastatic niches include myofibroblasts, immuno-inflammatory cells (macrophages), adipocytes, blood, and lymphatic vascular networks. Several studies have highlighted the adipocyte-macrophage interaction as a key driver of cancer progression and dissemination. The following two main classes of macrophages are distinguished: M1 (pro-inflammatory/anti-tumor) and M2 (anti-inflammatory/pro-tumor). These cells exhibit distinct microenvironment-dependent phenotypes that can promote or inhibit metastasis. On the other hand, obesity in cancer patients has been linked to a poor prognosis. In this regard, tumor-associated adipocytes modulate TME through the secretion of inflammatory mediators, which modulate and recruit tumor-associated macrophages (TAM). Hereby, this review describes the cellular and molecular mechanisms that link inflammation, obesity, and cancer. It provides a comprehensive overview of adipocytes and macrophages in the ECM as they control cancer initiation, progression, and invasion. In addition, it addresses the mechanisms of tumor anchoring and recruitment for M1, M2, and TAM macrophages, specifically highlighting their origin, classification, polarization, and regulatory networks, as well as their roles in the regulation of angiogenesis, invasion, metastasis, and immunosuppression, specifically highlighting the role of adipocytes in this process. [ABSTRACT FROM AUTHOR]

Tumorigenesis is a complex and dynamic process, consisting of three stages: initiation, progression, and metastasis. Tumors are encircled by extracellular matrix (ECM) and stromal cells, and the physiological state of the tumor microenvironment (TME) is closely connected to every step of tumorigenesis. Evidence suggests that the vital components of the TME are fibroblasts and myofibroblasts, neuroendocrine cells, adipose cells, immune and inflammatory cells, the blood and lymphatic vascular networks, and ECM. This manuscript, based on the current studies of the TME, offers a more comprehensive overview of the primary functions of each component of the TME in cancer initiation, progression, and invasion. The manuscript also includes primary therapeutic targeting markers for each player, which may be helpful in treating tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.