부산대학교 도서관

CD4+T cells that express the forkhead box P3 (FOXP3) transcription factor function as regulatory T (Treg) cells and hinder effective immune responses against cancer cells1,2,3. Abundant Tregcell infiltration into tumors is associated with poor clinical outcomes in various types of cancers3,4,5,6,7. However, the role of Tregcells is controversial in colorectal cancers (CRCs), in which FOXP3+T cell infiltration indicated better prognosis in some studies6,7,8,9. Here we show that CRCs, which are commonly infiltrated by suppression-competent FOXP3hiTregcells, can be classified into two types by the degree of additional infiltration of FOXP3lononsuppressive T cells10. The latter, which are distinguished from FOXP3+Tregcells by non-expression of the naive T cell marker CD45RA and instability of FOXP3, secreted inflammatory cytokines. Indeed, CRCs with abundant infiltration of FOXP3loT cells showed significantly better prognosis than those with predominantly FOXP3hiTregcell infiltration. Development of such inflammatory FOXP3lonon-Tregcells may depend on secretion of interleukin (IL)-12 and transforming growth factor (TGF)-β by tissues and their presence was correlated with tumor invasion by intestinal bacteria, especially Fusobacterium nucleatum.Thus, functionally distinct subpopulations of tumor-infiltrating FOXP3+T cells contribute in opposing ways to determining CRC prognosis. Depletion of FOXP3hiTregcells from tumor tissues, which would augment antitumor immunity, could thus be used as an effective treatment strategy for CRCs and other cancers, whereas strategies that locally increase the population of FOXP3lonon-Tregcells could be used to suppress or prevent tumor formation.