Tumor microenvironment (TME) is characterized by mutual interactions of the tumor, stromal and immune cells. Early and advanced colorectal tumors differ in structure and present altered serum cytokine levels. Mutual crosstalk among TME infiltrating cells may shift the balance into immune suppressive or pro-inflammatory, antitumor response this way influencing patients’ prognosis. Cancer-related inflammation affects all the body and this way, the systemic level of cytokines could reflect TME processes. Despite numerous studies, it is still not known how systemic cytokines levels change during colorectal cancer (CRC) tumor development. Better understanding tumor microenvironment processes could help in planning therapeutic interventions and more accurate patient prognosis. To contribute to the comprehension of these processes within TME, we reviewed cytokines levels from clinical trials in early and advanced colorectal cancer. Presented data were analyzed in the context of experimental studies and studies analyzing tumor infiltration with immune cells. The review summarizes clinical data of cytokines secreted by tumor microenvironment cells: lymphocytes T helper 1 (Th1), lymphocytes T helper 2 (Th2), lymphocytes T helper 17 (Th17), regulatory T cells (Treg cells), regulatory T cells (Breg cells), M1/M2 macrophages, N1/N2 neutrophils, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), innate lymphoid cells (ILC) natural killer (NK) cells and tumor cells.
The results of the latest research more and more bind development of neoplasms with the chronic inflammation. Inflammatory process creates microenvironment promoting development of neoplasms; as a result, malignant process start to develop in places, where chronic inflammation proceeds or regeneration of tissues takes place. Inflammatory cells not only create suitable microenvironment for development of neoplasms, but also excrete number of cytokines and growth factors promoting survival of a neoplasmatic cell and avoiding its apoptosis, promoting neoangiogenesis and metastases formation. Moreover, cytokines and other pro-inflammatory factors modulate expression of genes important in cancerogenesis, they also activate NFκB-dependent signaling pathways, which favor neoplasmatic cells to avoid apoptosis. On the other hand, oxidative stress accompanying chronic inflammation may promote mutagenesis, enabling that way the neoplasm development. The same cells and metabolic pathways are engaged in inflammatory and neoplasmatic processes, and development of cancer may be a consequence of loss of control over tissue regeneration during resolution of chronic inflammation. The role of most important cells and metabolic pathways in inflammatory process, which may lead to colon cancer, was discussed in this paper.
Aim: Comparison of 14 cytokines levels between a control group and prospectively enrolled CRC patients to confirm their significance in CRC development. We tested if a model based on 14 cytokines levels could predict prognosis in Caucasian CRC patients treated with 5-FU based chemotherapy. Background: Novel prognostic tools in colorectal cancer (CRC) are necessary to optimize treatment, reduce toxicity and chemotherapy (CHT) costs.
Over 50 human chemokines are known at present; the number of the newly discovered compounds from this group still grows. These proteins of low molecular weight, belonging to the family of cytokines with chemotactic properties. Chemokines participate in the physiological and pathological processes of the organism. Recent papers show their role in the processes of embryogenesis, organogenesis, allergies, wound healing, angiogenesis and apoptosis, the course of viral and bacterial infections, autoimmune diseases and cancerogenesis. Chemokines play crucial role in activation and migration of immune cells. Being a key player in chronic inflammation, chemokines may interfere the processes of cellular differentiation and contribute to loss of control over proliferation. Coexistence of inflammatory and cancerogenesis processes, impact of chemokines on cells associated with the tumor and stromal cells, mechanisms of immunological escape is considered to be a current scientific issue. Newly discovered functions of chemokines may reveal their new roles and create the new therapeutic perspectives. It is important to understand the relationship between the structure and function of chemokine receptors, the regulation of their signaling pathways and the genetic and epigenetic mechanisms that regulate the expression of chemokines and their receptors. This article presents the current state of knowledge regarding the construction and classification of chemokines and summarizes the most prominent roles of chemokines. Chemokines are still the subject of many scientific studies, new functions are being discovered. It gives an opportunity to limit the development of many dangerous diseases.
The prediction of colorectal cancer (CRC) response to palliative chemotherapy (CTH) is still difficult. Patients at a higher risk of progression may benefit from more aggressive treatment. This study assessed the predictive value of prolactin (PRL) and a panel of cytokines, chemokines, and growth factors for the risk of rapid progression in CRC patients starting palliative CTH. This study included 51 CRC patients initiating palliative CTH with up to 5-year follow-up, divided into rapid and non-rapid progressors. Serum samples were collected before CTH for assessment of a large panel of cytokines, chemokines, growth factors, and PRL via a multiplex method. Rapid progressors (N = 19) were characterized by increased baseline values of IL-8 and IP10 but decreased PRL levels. In addition, PRL below 18.2 ng/mL was a strong predictor of weight loss during CTH. Grade 3 (HR = 2.97; 95%CI: 1.48–5.98) and PRL level (HR = 0.96; 95%CI: 0.91–1.01) were independent risk factors of progression. We showed that CRC rapid progressors are characterized by decreased baseline PRL levels. In addition, increased baseline levels of IP-10, sHER-2, IL-6, and IL-8 may be associated with longer survival; however, larger studies are needed to confirm their predictive role in CRC patients.
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