通过定量分析肿瘤内 CD103+免疫细胞的丰度，鉴定人乳头瘤病毒相关性口咽癌患者的预后良好亚群。

Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance.

机构信息

Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.

Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.

出版信息

Ann Oncol. 2019 Oct 1;30(10):1638-1646. doi: 10.1093/annonc/mdz271.

DOI:10.1093/annonc/mdz271

PMID:31400196

Abstract

BACKGROUND

Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC.

PATIENTS AND METHODS

The abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis.

RESULTS

High intratumoral abundance of CD103+ immune cells using a ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs.

CONCLUSION

Quantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies.

摘要

背景

需要准确地对人乳头瘤病毒相关口咽癌（HPV+OPSCC）进行预后分层，以确定可能适合治疗强度降低的患者。我们在两个独立的 HPV+OPSCC 患者队列中评估了表面标志物 CD103 的预后意义，该标志物与组织驻留记忆 T 细胞（TRM）相关。

患者和方法

使用免疫组织化学定量检测 189 例接受根治性治疗的 HPV+OPSCC 患者队列中 CD103+免疫细胞的丰度和分布，并将其与结局相关联。然后使用单变量和多变量分析在包含 177 例 HPV+OPSCC 的独立队列中验证了这些发现。通过多光谱荧光免疫组织化学和基因表达分析对肿瘤内 CD103+免疫细胞进行了表征。

结果

在 HPV+OPSCC 患者的训练队列中，使用 ≥30%的截断值发现，19.8%的肿瘤中存在高肿瘤内 CD103+免疫细胞丰度，与总生存（OS）的良好预后相关，调整后的风险比（HR）为 0.13（95%置信区间 0.02-0.94，P=0.004）。在 HPV+OPSCC 的独立队列中，20.4%的肿瘤内存在高 CD103 丰度，OS 的调整 HR 为 0.16（95%置信区间 0.02-1.22，P=0.02）。两个队列中，高肿瘤内 CD103 的患者 5 年 OS 均为 100%。在两个队列中，加入肿瘤内 CD103+细胞丰度后，包含分期和年龄的多变量预后模型的 C 统计量显著提高。基于空间位置、CD8 和 CD69 的共表达以及基因表达谱，肿瘤内 CD103+细胞与 TRM 一致。