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.

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. Novel prognostic tools in colorectal cancer (CRC) are necessary to optimize treatment, reduce toxicity and chemotherapy (CHT) costs. We assessed prognostic significance of 14 cytokines: IL-1 beta, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL12p70, IL-13, IL-17A in 75 prospectively enrolled CRC patients before initiation of palliative or adjuvant CHT and in 22 control subjects. Readings were taken using the Bio-Plex 200 System. Response to treatment was assessed after 6 months from initiation of CHT. The treated group was divided depending on the response into a progressors (death, progression of disease) and non-progressors group (stable disease, partial response, complete response). We found that increased concentration of IL-8 was a negative prognostic factor in the whole group and palliative subgroup, whereas increased level of IL-10, IL-7, and IL-12p70 was a negative predictor in the adjuvant group CHT. We proposed a statistical model based on circulating cytokine levels, showing a good prognostic value in prediction of the response to CHT (AUC = 0.956). The model, including combined IL-2, IL-8, IL-10 and IL-13 levels, established in the whole treated group, should be validated in larger trials.

Background and Objectives: Soluble cell adhesion molecules (sCAMs) play a significant role in the metastatic potential of breast cancer (BC). They might block lymphocytes and promote angiogenesis and migration of cancer cells. We assessed the usefulness of sCAMs in the prognosis and monitoring of the progression of advanced BC. Materials and Methods: We assessed soluble E-selectin, P-selectin, VCAM-1, ICAM-1, EpCAM, IL-6Ra, TNF-R1, and TNF-R2 in 39 women with aBC. Blood samples were obtained at the beginning of the treatment and after 2 months. Results: The median progression-free survival (PFS) was 9 months, and overall survival (OS) was 27 months. The higher levels of sICAM-1 (HR = 2.60, p = 0.06) and lower levels of sEpCAM (HR = 2.72, p < 0.05) were associated with faster progression of aBC. High levels of sEpCAM through the follow-up period were significantly associated with a lower risk of progression (HR = 0.40, p < 0.01). We found the independent predictive value of higher than median sICAM-1 levels for PFS (HR = 2.07, p = 0.08) and of sVCAM-1 levels for OS (HR = 2.59, p < 0.05). Conclusions: Our data support the predictive value of sICAM-1 and sVCAM-1 and suggest that they could become markers for tailoring new therapies in aBC. sEpCAM level could be used as an early indicator of response to the therapy.

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.

Background: The predictive role of vitamin D (VD) in breast cancer (BC) patients’ survival is still being investigated. This paper aims to evaluate the changes in VD metabolites during chemotherapy (CTH) and the predictive role of VD status in Caucasian BC patients treated with CTH. Methods: Vitamin D and its metabolites were assessed with reference LC–MS/MS methodology in 98 consecutive BC patients starting CHT, after 3 and 6 months, and compared to the control group. Results: The frequency of VD deficiency in BC patients was greater than in the control group (56.1% vs. 37.2%). After 6 months of CTH, the number of VD-deficient BC patients slightly increased to 60%. The concentrations of VD active forms [25(OH)D₂, 25(OH)D₃], and catabolites [24,25(OH)₂D₃ and 3-epi-25(OH)D₃] decreased after 3 and 6 months of CTH compared to the baseline values. Strong positive correlations between concentrations of 3-epi-25(OH)D₃ and 25(OH)D in both groups were found. Similar correlations were also observed between 24,25(OH)₂D₃ and 25(OH)D levels. Kaplan–Meier survival analysis showed significantly longer survival in BC patients without deficiency (>20 ng/mL) at baseline (HR = 2.44 (95% CI 1.07–5.59), p = 0.026). Conclusions: (1) Our data provide further evidence that BC patients before CTH are more VD-deficient than the general population and this deficiency increases further during CTH treatment, as observed using the reference LC-MS methodology. (2) Presented results show that VD catabolism is not affected in BC patients. (3) The poorer survival in VD-deficient BP patients supports the importance of VD supplementation in BC patients with 25(OH)D levels below 20 ng/mL.

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.