Tumor-infiltrating FoxP3+ Tregs predict favorable outcome in colorectal cancer patients: A meta-analysis

Abstract

FoxP3⁺ regulatory T cells (FoxP3⁺ Tregs) are considered to be a key mediator in immune escape and tumor progression. However, the role of FoxP3⁺ Tregs in human colorectal cancer (CRC) remains controversial. Herein, we conducted a meta-analysis including 17 published studies with 3811 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating FoxP3⁺ Tregs in human CRC. We found FoxP3⁺ Tregs infiltrating into both intraepithelium and stroma within tumor were significantly positively correlated with 1, 3, 5 and 10-year overall survival (OS), but not with 1, 3, 5-year disease-free survival (DFS) of patients. Interestingly, in stratified analyses by compartments within tumor FoxP3⁺ Tregs infiltrating into, FoxP3⁺ Tregs invading stromal compartment significantly improved 3 and 5-year OS, yet OS wasn’t improved when FoxP3⁺ Tregs infiltrated into intraepithelium only. Furthermore, FoxP3⁺ Tregs invading both intraepithelium and stroma significantly inversely correlated with TNM stage of CRC. In conclusion, High density of FoxP3⁺ Tregs within tumor especially at stromal compartment leads to a favorable outcome in CRC, implicating FoxP3⁺ Tregs are one of valuable indexes for prognostic prediction in human CRC.