Department of Otolaryngology, University of Miami, Miller School of Medicine, Miami, Florida, United States of America ; Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, United States of America.
PLoS One. 2013 Aug 20;8(8):e71908. doi: 10.1371/journal.pone.0071908. eCollection 2013.
Forkhead box protein P3 (FOXP3) expression in tumor infiltrating CD4(+)T cells is generally associated with an intrinsic capacity to suppress tumor immunity. Based on this notion, different studies have evaluated the prognostic value of this maker in cancer but contradictory results have been found. Indeed, even within the same cancer population, the presence of CD4(+)FOXP3(+)T cells has been associated,with either a poor or a good prognosis, or no correlation has beenfound. Here, we demonstrate,in patients with oral squamous cell carcinoma (OSCC), that what really represents a prognostic parameter is not the overall expression of FOXP3 but its intracellular localization.While overallFOXP3 expression in tumor infiltrating CD4(+)T cells does not correlate with tumor recurrence, its intracellular localization within the CD4 cells does: nuclear FOXP3 (nFOXP3) is associated with tumor recurrence within 3 years, while cytoplasmicFOXP3 (cFOXP3) is associated with a lower likelihood of recurrence. Thus, we propose elevated levels of the cFOXP3/nFOXP3 ratio within tumor infiltrating CD4(+) T cells as a predictor of OSCC recurrence.
叉头框蛋白 P3（FOXP3）在肿瘤浸润性 CD4（+）T 细胞中的表达通常与内在抑制肿瘤免疫的能力相关。基于这一概念，不同的研究已经评估了该标志物在癌症中的预后价值，但得到了相互矛盾的结果。事实上，即使在同一癌症人群中，CD4（+）FOXP3（+）T 细胞的存在也与预后不良或良好相关，或者没有相关性。在这里，我们在口腔鳞状细胞癌（OSCC）患者中证明，真正代表预后参数的不是 FOXP3 的总体表达，而是其细胞内定位。虽然肿瘤浸润性 CD4（+）T 细胞中 FOXP3 的总体表达与肿瘤复发无关，但 FOXP3 在 CD4 细胞内的细胞内定位与之相关：核 FOXP3（nFOXP3）与 3 年内肿瘤复发相关，而细胞质 FOXP3（cFOXP3）与复发可能性较低相关。因此，我们提出肿瘤浸润性 CD4（+）T 细胞中 cFOXP3/nFOXP3 比值升高可作为 OSCC 复发的预测指标。
