Abstract
ObjectiveThe mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC.MethodsFlow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher’s exact test and non-parametric Wilcoxon’s matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC.ResultsWe found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels.ConclusionThe mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.
Highlights
Colorectal cancer (CRC) is one of the most common malignant tumors, with an estimated 1.8 million new cases worldwide in 2018 and ranks third with regard to incidence and second with regard to mortality [1]
We investigated the immune landscape of the mesentery, the role of lymphocytes and its association with the clinicopathological characteristics of CRC
We found that immune cells in the normal mesentery were mainly of lymphoid lineage
Summary
Colorectal cancer (CRC) is one of the most common malignant tumors, with an estimated 1.8 million new cases worldwide in 2018 and ranks third with regard to incidence and second with regard to mortality [1]. Studies have shown that postoperative recurrence was associated with cancer-related death in most cases [2,3,4], and mortality rates were 3.47-fold higher in patients with CRC recurrence than in those who were recurrence-free [5]. Metastatic cancer cells were detected in the colorectal mesentery in approximately 20% of patients with CRC, who underwent radical surgery [9, 10], and patients with mesenteric metastasis tend to show poor cumulative survival rates [11, 12]. Following intestinal inflammation, most immune cells detected in the mesenteric adipose tissue comprise pro-inflammatory cells, such as M1 macrophages [17]. Lymphocyte composition and phenotype in the mesenteric immune microenvironment remain unclear
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