Knops Alexander M, South Andrew, Rodeck Ulrich, Martinez-Outschoorn Ubaldo, Harshyne Larry A, Johnson Jennifer, Luginbuhl Adam J, Curry Joseph M
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States.
Department of Dermatology, Thomas Jefferson University, Philadelphia, PA, United States.
Front Oncol. 2020 Nov 27;10:565306. doi: 10.3389/fonc.2020.565306. eCollection 2020.
The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor microenvironment (TME). Among the most abundant of these stromal cells are cancer-associated fibroblasts (CAFs). While their contribution to tumor progression is widely acknowledged, and various CAF-targeted treatments are under development, the relationship between CAF density and the clinicopathologic course of HNSCC has not been clearly defined. Here we examine the published evidence investigating the relationship of cancer-associated fibroblasts to local recurrence and indicators of prognostic significance in HNSCC.
We conducted a meta-analysis of existing publications that compare the relationship between CAF density, local recurrence, and clinically significant pathologic criteria of disease development (T stage, nodal positivity, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation). Thirteen studies met the selection criteria, providing a total study population of 926 patients. Forest plots and risk ratios were generated to illustrate overall relationships.
Higher CAF density within the tumor microenvironment is associated with advanced T stage, nodal infiltration, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation (p <0.05). High CAF density is also associated with increased rates of local recurrence (p <0.001).
Across multiple studies, increased CAF density is correlated with histopathological criteria of poor prognosis in HNSCC. These findings highlight that CAFs may play a pivotal role in HNSCC development and progression. Staining for CAFs may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment. Understanding the mechanisms by which CAFs reciprocally interact with cancer cells will be crucial for optimization of TME-focused treatment of HNSCC.
头颈部鳞状细胞癌（HNSCC）的进展和临床病程依赖于肿瘤微环境（TME）中癌细胞与基质细胞之间的复杂相互作用。这些基质细胞中最丰富的是癌症相关成纤维细胞（CAF）。虽然它们对肿瘤进展的贡献已得到广泛认可，并且各种针对CAF的治疗方法正在研发中，但CAF密度与HNSCC临床病理病程之间的关系尚未明确界定。在此，我们研究已发表的证据，以探讨癌症相关成纤维细胞与HNSCC局部复发及预后相关指标之间的关系。
我们对现有出版物进行了荟萃分析，比较CAF密度、局部复发以及疾病发展的临床重要病理标准（T分期、淋巴结阳性、临床分期、血管侵犯、神经周围侵犯、Ki67表达和分化）之间的关系。13项研究符合选择标准，提供了总共926例患者的研究群体。生成森林图和风险比以说明总体关系。
肿瘤微环境中较高的CAF密度与晚期T分期、淋巴结浸润、临床分期、血管侵犯、神经周围侵犯、Ki67表达和分化相关（p<0.05）。高CAF密度也与局部复发率增加相关（p<0.001）。
在多项研究中，CAF密度增加与HNSCC预后不良的组织病理学标准相关。这些发现突出表明CAF可能在HNSCC的发生和进展中起关键作用。对CAF进行染色可能是当前病理分析的一项有价值的补充，并有助于指导预后和治疗。了解CAF与癌细胞相互作用的机制对于优化以TME为重点的HNSCC治疗至关重要。
