Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Department of Pathology, University Hospital of Wales, Cardiff, UK.
Mucosal Immunol. 2014 Mar;7(2):428-39. doi: 10.1038/mi.2013.62. Epub 2013 Sep 25.
Although elevated CD4⁺Foxp3⁺ regulatory T cell (Treg) frequencies within tumors are well documented, the functional and phenotypic characteristics of CD4⁺Foxp3⁺ and CD4⁺Foxp3⁻ T cell subsets from matched blood, healthy colon, and colorectal cancer require in-depth investigation. Flow cytometry revealed that the majority of intratumoral CD4⁺Foxp3⁺ T cells (Tregs) were Helios⁺ and expressed higher levels of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD39 than Tregs from colon and blood. Moreover, ∼30% of intratumoral CD4⁺Foxp3⁻ 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-β (TGF-β), and was ∼50-fold more suppressive than Foxp3⁺ Tregs. Thus, intratumoral Tregs are diverse, posing multiple obstacles to immunotherapeutic intervention in colorectal malignancies.
尽管肿瘤内 CD4⁺Foxp3⁺调节性 T 细胞（Treg）频率升高已有充分记录，但来自匹配的血液、健康结肠和结直肠癌的 CD4⁺Foxp3⁺和 CD4⁺Foxp3⁻T 细胞亚群的功能和表型特征仍需要深入研究。流式细胞术显示，大多数肿瘤内 CD4⁺Foxp3⁺T 细胞（Tregs）为 Helios⁺，并且表达更高水平的细胞毒性 T 淋巴细胞抗原 4（CTLA-4）和 CD39，高于结肠和血液中的 Tregs。此外，约 30%的肿瘤内 CD4⁺Foxp3⁻T 细胞表达与调节功能相关的标志物，包括潜伏期相关肽（LAP）、淋巴细胞激活基因-3（LAG-3）和 CD25。该独特的细胞群产生白细胞介素-10（IL-10）和转化生长因子-β（TGF-β），其抑制作用比 Foxp3⁺Treg 强约 50 倍。因此，肿瘤内 Tregs 具有多样性，这对结直肠恶性肿瘤的免疫治疗干预构成了多重障碍。
