Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3+ T regulatory cells in colorectal cancer

Abstract

Background The prognostic value of intratumor T regulatory cells (Tregs) in colorectal cancer (CRC) was previously reported, but the role of these cells in tumor draining lymph nodes (TDLNs) was less addressed. Methods A total of 150 CRC stages I-IV were retrospectively enrolled. Intratumor and TDLN Tregs were examined by immunohistochemical assay. The association of these cells was estimated by Pearson correlation. Survival analyses of subgroups were conducted by Kaplan–Meier curves, and the log-rank test and risk factors for survival were tested by the Cox proportional hazard model. Results High accumulation of Tregs in tumors was significant in patients with younger age and good histological grade, where enrichment of these cells in TDLNs was more apparent in those with node-negative disease and early TNM stage disease, both of which were more common in early T stage cases. A significant correlation of intratumoral and TDLN Tregs was detected. Patients with higher intratumoral Tregs displayed significantly better PFS and OS than those with lower Tregs. However, no such differences were found, but a similar prognostic prediction trend was found for these cells in TDLNs. Finally, intratumoral Tregs were an independent prognostic factor for both PFS (HR = 0.97, 95% CI 0.95–0.99, P < 0.01) and OS (HR = 0.98, 95% CI 0.95–1.00, P = 0.04) in the patients. Conclusions Higher intratumor Tregs were associated with better survival in CRC. Although no such role was found for these cells in TDLNs, the positive correlation and similar prognostic prediction trend with their intratumoral counterparts may indicate a parallelized function of these cells in CRC.

BICDL1 Predicts Poor Prognosis and is Correlated with Methylation and Immune Infiltration in Colorectal Cancer

“…High levels of Treg infiltration in patients are associated with poor prognosis. 35 Several studies 36 , 37 have reported that Tregs inhibit the immune response by competing for CD80 and CD86 activation signals via cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which has high expression on the cell surface, and high affinity receptor CD25 competes for IL-2 binding and promotes cytokines secretion, such as IL-35, TGF-β and IL-10. Our findings indicate that BICDL1 is correlated with Treg and IL2, and BICDL1 may regulate CRC progression by affecting Treg and IL2.…”