Feng Zipei, Bethmann Daniel, Kappler Matthias, Ballesteros-Merino Carmen, Eckert Alexander, Bell R Bryan, Cheng Allen, Bui Tuan, Leidner Rom, Urba Walter J, Johnson Kent, Hoyt Clifford, Bifulco Carlo B, Bukur Juergen, Wickenhauser Claudia, Seliger Barbara, Fox Bernard A
Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Portland, Oregon, USA.
Department of Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA.
JCI Insight. 2017 Jul 20;2(14). doi: 10.1172/jci.insight.93652.
Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3+, CD8+, FoxP3+, CD163+, and PD-L1+ cells using multispectral imaging was performed on sections from 119 patients with HPV- OSCC. Expression of β2-microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome. We found that, consistent with previous reports, high numbers of CD8+ T cells at the invasive margin correlated significantly with prolonged overall survival (OS), while the number of FoxP3+ or PD-L1+ cells did not. Compiling the number of FoxP3+ or PD-L1+ cells within 30 μm of CD8+ T cells identified a significant association with a high number of suppressive elements close to CD8+ T cells and reduced OS. Integrating this information into a cumulative suppression index (CSI) increased correlation with OS. Incorporating tumor expression levels of APM components with CSI further improved prognostic power. This multiparametric immune profiling may be useful for stratifying patients with OSCC for clinical trials.
评估T淋巴细胞频率可为口腔鳞状细胞癌(OSCC)患者提供预后信息。然而,同时评估T细胞频率以及评估抑制性元件和抗原加工机制(APM)缺陷的效果尚未明确。使用多光谱成像对119例HPV阴性OSCC患者的切片进行CD3 +、CD8 +、FoxP3 +、CD163 +和PD-L1 +细胞的同时表征。对β2-微球蛋白、MHC I类重链和大型多功能肽酶10的表达进行定量,所有数据均与患者预后相关。我们发现,与先前报道一致,侵袭边缘大量的CD8 + T细胞与延长的总生存期(OS)显著相关,而FoxP3 +或PD-L1 +细胞的数量则不然。汇总CD8 + T细胞30μm范围内FoxP3 +或PD-L1 +细胞的数量,发现与靠近CD8 + T细胞的大量抑制性元件和缩短的OS存在显著关联。将该信息整合到累积抑制指数(CSI)中可增加与OS的相关性。将APM成分的肿瘤表达水平与CSI相结合可进一步提高预后能力。这种多参数免疫谱分析可能有助于对OSCC患者进行分层以开展临床试验。