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.

Keywords: colorectal cancer; cytokine; inflammation; tumor microenvironment.

Figure 1

Several cell types in tumor histology were found to be associated with poor patient outcomes. These cells include M2 tumor-associated macrophages, N2 neutrophils, MDSCs (myeloid-derived suppressor cells), regulatory T cells (Treg cells), subsets of T helper lymphocytes: Th2, Th9, and Th17 cells, cancer-associated fibroblasts (CAF), and regulatory B cells (Breg) cells playing mostly tumor-promoting functions. Other cells in TME showed antitumor activity related to a favorable prognosis. This group of cells includes tumor associated macrophages of M1 phenotype, N1 neutrophils, Th1 cells, cytotoxic T cells, innate lymphoid cells (ILC) with natural killer (NK cells) cells. Some cells subtypes, like Th9, Th17, Th22 may play a dual, pro-tumor, or antitumor role depending on the TME polarization. Mutual crosstalk among TME cells may shift the balance into immune suppressive or antitumor immunity, this way influencing patients’ prognosis.