Local and systemic Th17 immune response associated with advanced stage colon cancer.

ABSTRACT

BACKGROUND: Little is known about how the immunologic microenvironment changes during tumor progression and metastatic spread. Recently, murine models have shown the T-helper 17 (Th17) pathway to play an important role in promoting colorectal cancer (CRC). The purpose of this study was to compare cytokine profiles in the tumor microenvironment of CRC between local disease (stages I/II) and advanced disease (stages III/IV), and to determine whether these changes were manifest in the systemic circulation of patients with advanced disease. MATERIALS AND METHODS: Serum and tissue cytokine profiles were assayed among patients with documented adenocarcinoma before surgical resection at a single institution from September 2014 to February 2015. Using the Bio-Plex Pro Human Th17 Cytokine Assay Kit (Bio-Rad Laboratories), the concentrations of multiple cytokines were determined. Multiple logistic regression analyses were used to evaluate the association between TNM staging and cytokine levels. RESULTS: A total of 33 patients with documented adenocarcinoma were included. None of the patients received neoadjuvant chemotherapy. American Joint Commission on Cancer TNM classification was used. Advanced disease was associated with elevated tumor levels of tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, IL-17A, and IL-17F, and only stage IV showed elevated systemic levels of Th17-associated cytokines IL-17F, IL-23, and IL-25. CONCLUSIONS: The Th17 pathway likely has important mechanistic implications in human CRC. Metastatic disease was associated with elevated Th17-associated cytokines both in colonic tissue and systemically. These changes in systemic expression of Th17-associated cytokines could establish novel pathways for CRC and warrant further investigation.