Impact Of Circulating T Helper 1 And 17 Cells in the Blood on Regional Lymph Node Invasion in Colorectal Cancer

Abstract

We hypothesised that the blood levels of immune cells would be related to the progression of colorectal cancer and regional lymph node metastasis. We investigated the association between the blood levels of immune cells and regional lymph node metastasis in colorectal cancer patients. Patients with American Joint Committee on Cancer (AJCC) stages 1 and 2 colorectal cancer were assigned to Early stage group and those with AJCC stages 3 and 4 were assigned to Late stage group. Blood levels of circulating immune cells, such as cluster of differentiation (CD)4+ including T helper 1 (Th1) and 17 (Th17) cells, regulatory T (Treg) cells, CD8+ T cells, and natural killer (NK) cells were assessed using fluorescence-activated cell sorting (FACS). The blood levels of CD4+ T, Treg, CD8+ T, and NK cells did not significantly differ between the two groups. However, the blood levels of Th1 and Th17 cells did significantly differ between the groups. Specifically, Late stage group had higher levels of Th1 and Th17 cells than Early stage group (Th1, 11.14±1.22% vs. 16.25±1.57%, p = 0.015; Th17, 3.32±0.05% vs. 1.11±0.15%, p < 0.01). In conclusion, the blood levels of Th1 and Th17 cells significantly increased as the N stage increased. The blood levels of Th1 and Th17 cells might be useful as predictive markers of lymph node invasion in colorectal cancer.

Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer

“…Finally, Th17 cells that are endowed with strong inflammatory properties by virtue of their IL-17 and IL-21 production, were found at higher proportions in the tumor as well as in the blood of CRC patients relative to healthy volunteers (45,49). In addition, a high amount of Th17 was associated with tumor progression and a poor prognosis (12,13,55). While the mechanisms involving Th17 in CRC are not completely understood, these cells could act through the release of IL-17 as poor prognosis has been reported for patients with high levels of IL-17 (56,57).…”

“…These observations could explain, at least in part, disease progression in a significant subset of patients with MSI tumors having received checkpoint inhibitors. Although the clinical outcome of patients enrolled in clinical studies blocking immune checkpoints does not seem to be influenced by Lynch Syndrome so far, no study seems to have investigated the association between CMS and response to checkpoint inhibitors yet (55,126).…”

Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated with Attenuation of Colonic Inflammation and Protection Against Colorectal Cancer

“…For example, we have shown that activation of AhR by dietary indoles in a delayed-type hypersensitivity (DTH) model is essential for shifting the T cell response from a proinflammatory Th17 to an anti-inflammatory Treg phenotype [76]. This is important in regards to CRC as studies have shown that high expression of Tregs in CRC patients indicate a more favorable prognosis [77,78], whereas increased Th17 has been linked to CRC pathogenicity and tumor development [79][80][81]. The current report reinforces this notion, as gene expression data of CRC patients seemed to indicate that high expression of anti-inflammatory T cell factors (FoxP3, IL-10) improved patient survival, whereas proinflammatory makers linked to Th17 and Th1 phenotypes decreased overall survival in the patient population.…”

Perioperative Changes in Lymphocyte Subpopulations in Patients Undergoing Surgery for Colorectal Cancer

“…Lee et al . report that higher levels of Th17 might be useful as markers of lymph node invasion ( 13 ). In our group, only two patients had lymph node invasion, thus it was too small to verify this hypothesis.…”