Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Abstract

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.

Evaluation of the Effects of Genistein In Vitro as a Chemopreventive Agent for Colorectal Cancer—Strategy to Improve Its Efficiency When Administered Orally

“…In CRC, cytokines play a crucial role in the development of this type of cancer. However, the available data are insufficient to describe the changes in the cytokine profile during the development of CRC, as well as the mechanisms that lead to changes in the cytokine levels in this type of cancer [ 59 ]. In the SW620 cell line, a significant increase was observed, compared to the control, after treatment for 24 h with genistein in the cytokines IL-1beta, IL-2, IL-6, IL-13, IL-17A, IL-27, and GM-CSF.…”

“…Its presence in tumors can influence the activation of the immune system and predict a better prognosis. It has been shown mainly with antitumor properties in CRC [ 59 ]. Additionally, both IL-5 and GM-CSF could control tumor growth, since the negative regulation of IL-5 and GM-CSF has been shown to increase tumor burden in a murine model of CRC [ 66 ].…”

“…Several studies have shown discrepancies in the antiproliferative effect of these cytokines in various cell lines and CRC clinical studies [ 70 ]. These interleukins can have both pro- and antitumor functions, depending on the tumor microenvironment, and among these functions, a possible inhibitory effect on CRC has been described [ 59 ].…”

“…IL-10 is also an immunomodulatory cytokine that exhibits both pro- and antitumor characteristics, depending on the tumor microenvironment, showing its behavior in the pathogenesis and progression of CRC [ 77 ]. Perhaps one of its main roles is tumor suppression [ 59 ]. Associated with this description, IL-10 has been described with antitumor activity in the tumor microenvironment and with neovascularization inhibitory activity in a murine model, fulfilling a role in the suppression of tumor growth [ 78 ].…”

Overexpression of Interleukin-8 and Interleukin-13 as potent immune markers associated with survival and dietary habits in esophageal squamous cell carcinoma

“…It is also associated with the development of different types of cancer like lung cancer, prostate cancer, breast cancer, colorectal cancer, etc. [8,11]. It plays .…”