Distribution of regulatory T-cells and other phenotypes of T-cells in tumors and regional lymph nodes of colorectal cancer patients

Abstract

Background/Aim: Tumor microenvironments consist of many types of immune cells, in which regulatory T-cells (Tregs) are supposed to play important roles to suppress antitumor immunity. Regional lymph nodes are essential for antitumor immunity in colorectal cancer (CRC). In this study, we compared the diversity of phenotypes of T-cells in normal tissue and regional lymph nodes in order to determine the immunosuppressive mechanism of lymph node metastasis of CRC. Patients and Methods: Fifty patients were enrolled in this study, and paired samples (tumor tissue, normal tissue, and three regional lymph node samples and as well as non-regional lymph node samples) were obtained from each patient. In each paired-sample set, the proportions of different immune cell types and T-cells expressing immune checkpoint molecules were compared using flow cytometry. Results: Higher proportions of Tregs [7.58% (4.94%-13.87%) vs. 1.79% (0.03%-5.36%), p<0.001] and lower proportions of INFγ- producing CD4-positive T (iCD4+) cells [21.49% (12.08%- 27.35%) vs. 26.55% (15.65%-37.63%), p<0.001] were observed in tumor tissue than in normal mucosa. Parts of regional lymph nodes nearest the tumor had a greater proportion of Tregs [5.86% (4.18%-7.69%)] and lower proportions of iCD4+ [5.94% (3.51%-9.04%)] and INFγ- producing CD8-positive T (iCD8+) cells [21.93% (14.92%- 35.90%)] than distant parts of regional lymph nodes and nonregional lymph nodes. Both immune-suppressing molecules (CTLA-4 and PD-1) and immune-promoting molecules (OX-40 and ICOS) tended to be highly expressed in tumor tissue and local lymph nodes. Conclusion: In patients with CRC, regional lymph nodes, especially the parts nearest the tumor, had a higher proportion of Tregs and other suppressive immunophenotypes of T-cells than those located more distantly.