下咽癌中与人类乳头瘤病毒（HPV）及临床结局相关的免疫相关蛋白和肿瘤浸润性CD8 +淋巴细胞
Immune related proteins and tumor infiltrating CD8+ lymphocytes in hypopharyngeal cancer in relation to human papillomavirus (HPV) and clinical outcome.
作者信息
Landin David, Ährlund-Richter Andreas, Mirzaie Leila, Mints Michael, Näsman Anders, Kolev Aeneas, Marklund Linda, Dalianis Tina, Munck-Wikland Eva, Ramqvist Torbjörn
机构信息
Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Otorhinolaryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Head Neck. 2020 Nov;42(11):3206-3217. doi: 10.1002/hed.26364. Epub 2020 Jul 1.
BACKGROUND
Hypopharyngeal cancer (HPSCC) shows a poor clinical outcome, while HPSCC, caused by human papillomavirus (HPV), presents a better outcome. Here, HPCC, immune proteins, and tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were evaluated in relation to HPV and outcome.
METHODS
Fresh frozen tissue from four HPV-positive HPSCC, 39 HPV-negative HPSCC, and normal samples were analyzed for protein expression by the Proseek immuno-oncology immunoassay. CD8+ TIL numbers evaluated by immunohistochemistry on 144 formalin-fixed biopsies were analyzed in relation to clinical outcome.
RESULTS
Proteins differing between HPV-positive and negative HPSCC included CD8A, PD-L1, Fas ligand, and chemokines. High CD8+ TIL numbers were correlated to improve clinical outcome in HPV-negative HPSCC.
CONCLUSIONS
High expression of immune proteins in HPV-positive HPSCC may explain the better clinical outcome. CD8+ TILs are of relevance for outcome of HPV-negative HPSCC, while tumors with high immune activity but poor patient survival suggest a role for immune therapy.
背景
下咽癌（HPSCC）临床预后较差，而由人乳头瘤病毒（HPV）引起的下咽癌预后较好。在此，对HPV、预后与下咽癌、免疫蛋白以及肿瘤浸润性CD8 +淋巴细胞（CD8 + TILs）进行了评估。
方法
采用Proseek免疫肿瘤免疫分析法分析来自4例HPV阳性下咽癌、39例HPV阴性下咽癌的新鲜冷冻组织以及正常样本的蛋白表达。通过免疫组织化学对144例福尔马林固定活检样本评估CD8 + TIL数量，并分析其与临床预后的关系。
结果
HPV阳性和阴性下咽癌之间存在差异的蛋白包括CD8A、程序性死亡受体配体1（PD-L1）、Fas配体和趋化因子。在HPV阴性下咽癌中，高数量的CD8 + TIL与改善临床预后相关。
结论
HPV阳性下咽癌中免疫蛋白的高表达可能解释了较好的临床预后。CD8 + TILs与HPV阴性下咽癌的预后相关，而免疫活性高但患者生存率低的肿瘤提示免疫治疗的作用。
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