RESUMO
Although elevated CD4âºFoxp3⺠regulatory T cell (Treg) frequencies within tumors are well documented, the functional and phenotypic characteristics of CD4âºFoxp3⺠and CD4âºFoxp3â» T cell subsets from matched blood, healthy colon, and colorectal cancer require in-depth investigation. Flow cytometry revealed that the majority of intratumoral CD4âºFoxp3⺠T cells (Tregs) were Helios⺠and expressed higher levels of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD39 than Tregs from colon and blood. Moreover, â¼30% of intratumoral CD4âºFoxp3â» T cells expressed markers associated with regulatory functions, including latency-associated peptide (LAP), lymphocyte activation gene-3 (LAG-3), and CD25. This unique population of cells produced interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß), and was â¼50-fold more suppressive than Foxp3⺠Tregs. Thus, intratumoral Tregs are diverse, posing multiple obstacles to immunotherapeutic intervention in colorectal malignancies.