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.
Highlights
An increasing body of evidence supports the crucial role of cytokines in the development of colorectal cancer (CRC)
With known M2 predominance in the advanced CRC stage, increased levels of interleukin 10 (IL-10) in stage IV could be a result of M2 macrophages secretion [74,75] and myeloid-derived suppressor cells (MDSC) and Treg cells production, as the number of these cells increases with the tumor stage
interleukin 5 (IL-5) secreted by innate lymphoid cells type 2 (ILC2) is important for the development, recruitment, activation, and survival of eosinophils [255] associated with antitumor response and good CRC prognosis [256]
Summary
An increasing body of evidence supports the crucial role of cytokines in the development of colorectal cancer (CRC). Patients in various stages of colon cancer are characterized by different cytokine serum profiles [2]. There is a paucity of data regarding cytokines profile changes during the development of CRC as well as about mechanisms within the tumor leading to changes in the cytokine levels. The current review aimed to summarize available clinical data of chosen cytokines levels in early and advanced CRC stages. Systemic cytokine levels were presented according to clinical stages reported in original articles. Source papers reported CRC stages according to American Joint Committee on Cancer system, assessing tumor, nodes, and metastasis (TNM) in CRC patients. In stage III, lymph nodes are infiltrated with the cancer cells, but still, there are no distant metastasis. Stage IV patients suffer from advanced disease with metastasis present in distant organs
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