Aggarwal Sadhna, Sharma Suresh C, N Das Satya
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India.
J Surg Oncol. 2017 Dec;116(8):1103-1113. doi: 10.1002/jso.24782. Epub 2017 Aug 22.
The immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival.
The phenotypic and functional characteristics of Regulatory T (T ) CD4 CD25 FoxP3 subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-β) by Western blot and qRT-PCR.
An increased (P < 0.05) prevalence of T phenotypes (CD4 CD25 , CD4 FoxP3 , CD8 FoxP3 , CD4 CD25 FoxP3 ) was observed in the peripheral circulation of OSCC patients that positively correlated with clinicopathological features. The increased frequency of CD4 CD8 CD25 FoxP3 , a unique T cell subset, CTLA-4 , GITR , NrP1 , HLA-DR , CD127 , Tbet , TGF-β , and granzyme B (GzmB) T also showed a significantly higher prevalence in OSCC patients. Functionally, CD4 FoxP3 T showed skewed expression of IL-2, IL-10, and IL-35 in patients as compared with the normal controls. Further, enhanced expression of CCR5 and CCR7 on T with up regulation of their ligands (CCL5, CCL19, and CCL21) in tumor cells indicates efficient recruitment and trafficking of T to the tumor site.
It seems reasonable to assume that modulation of functional dynamics of selective T subsets may be useful in developing immunotherapeutic strategy for OSCC patients.
口腔鳞状细胞癌(OSCC)患者的免疫功能障碍是影响无病生存期的肿瘤生长和扩散的主要因素之一。
采用多色流式细胞术评估OSCC患者中调节性T(T)CD4 CD25 FoxP3亚群的表型和功能特征,并用蛋白质免疫印迹法和定量逆转录聚合酶链反应检测其效应成分(转化生长因子-β)。
在OSCC患者外周血循环中观察到T表型(CD4 CD25 、CD4 FoxP3 、CD8 FoxP3 、CD4 CD25 FoxP3 )的患病率增加(P < 0.05),且与临床病理特征呈正相关。独特的T细胞亚群CD4 CD8 CD25 FoxP3 、细胞毒性T淋巴细胞相关抗原4(CTLA-4)、糖皮质激素诱导的肿瘤坏死因子受体(GITR)、神经氨酸酶1(NrP1)、人类白细胞抗原DR(HLA-DR)、白细胞介素-7受体α链(CD127)、T盒转录因子(Tbet)、转化生长因子-β(TGF-β)和颗粒酶B(GzmB)T的频率增加,在OSCC患者中的患病率也显著更高。在功能上,与正常对照相比,患者中CD4 FoxP3 T显示白细胞介素-2、白细胞介素-10和白细胞介素-35表达失衡。此外,肿瘤细胞中T上趋化因子受体5(CCR5)和趋化因子受体7(CCR7)表达增强,其配体(CCL5、CCL19和CCL21)上调,表明T有效地募集和运输到肿瘤部位。
合理推测,调节选择性T亚群的功能动力学可能有助于为OSCC患者制定免疫治疗策略。