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人乳头瘤病毒阳性口咽癌中B细胞表达特征及预后意义

Characterising B cell expression and prognostic significance in human papillomavirus positive oropharyngeal cancer.

作者信息

Young Richard J, Angel Christopher, Bressel Mathias, Pizzolla Angela, Thai Alesha A, Porceddu Sandro V, Liu Howard, Idrizi Rejhan, Metta Jana, Lim Annette M, Solomon Benjamin J, Rischin Danny

机构信息

Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia.

Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.

出版信息

Oral Oncol. 2024 Mar;150:106687. doi: 10.1016/j.oraloncology.2024.106687. Epub 2024 Jan 22.

Abstract

OBJECTIVES

The incidence of human papillomavirus positive oropharyngeal cancer (HPV+OPC) is increasing, and new biomarkers are required to better define prognostic groups and guide treatment. Infiltrating T cells have been well studied in head and neck cancer, however the presence and role of B cells and tertiary lymphoid structures (TLS) in the tumor microenvironment has not, even though the interplay between T and B cells is increasingly being recognised.

MATERIALS AND METHODS

Using CD20 immunohistochemistry (IHC) to identify B cells and TLS in a cohort of 159 HPV + OPC patients, we semi-quantitatively scored abundance and location (intra-tumoral or stromal) and correlated findings with patient survival.

RESULTS

32% (51/157) of patients had high intra-tumoral (IT) abundance of CD20 B cells (≥5%) and this was prognostic for improved overall survival (OS) with an adjusted hazard ratio (HR) of 0.2 (95 % CI 0.0-0.7, p = 0.014). We validated our results in an independent cohort comprising 171 HPV + OPC where 14% (23/171) were IT CD20 high, again showing improved survival with an adjusted HR for OS of 0.2 (95 % CI 0.0-1.4, p = 0.003). Neither stromal abundance nor the presence of TLS were prognostic in either cohort. B cells were subtyped by multispectral IHC, identifying CD20CD27 cells, consistent with memory B cells, as the predominant subtype. Combined with validated biomarker CD103, a marker of tissue-resident memory T cells, IT CD20 B cells abundance was able to prognostically stratify patients further.

CONCLUSIONS

CD20 B cell abundance has the potential to be used as a biomarker to identify good and poor prognosis HPV + OPC patients.

摘要

目的

人乳头瘤病毒阳性口咽癌(HPV+OPC)的发病率正在上升,需要新的生物标志物来更好地定义预后分组并指导治疗。浸润性T细胞在头颈癌中已得到充分研究,然而肿瘤微环境中B细胞和三级淋巴结构(TLS)的存在及作用尚未得到研究,尽管T细胞和B细胞之间的相互作用越来越受到认可。

材料与方法

我们使用CD20免疫组织化学(IHC)来识别159例HPV+OPC患者队列中的B细胞和TLS,对半定量评分丰度和位置(肿瘤内或基质),并将结果与患者生存率相关联。

结果

32%(51/157)的患者肿瘤内(IT)CD20 B细胞丰度高(≥5%),这对改善总生存期(OS)具有预后意义,调整后的风险比(HR)为0.2(95%CI 0.0-0.7,p=0.014)。我们在一个包含171例HPV+OPC的独立队列中验证了我们的结果,其中14%(23/171)为IT CD20高表达,再次显示OS的调整后HR为0.2时生存率提高(95%CI 0.0-1.4,p=0.003)。在两个队列中,基质丰度和TLS的存在均无预后意义。通过多光谱IHC对B细胞进行亚型分类,确定CD20CD27细胞(与记忆B细胞一致)为主要亚型。结合经过验证的生物标志物CD103(组织驻留记忆T细胞的标志物),IT CD20 B细胞丰度能够进一步对患者进行预后分层。

结论

CD20 B细胞丰度有可能用作生物标志物,以识别HPV+OPC患者的预后好坏。

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