CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
HIV 和致癌性人乳头瘤病毒对阴茎鳞状细胞癌肿瘤免疫微环境的影响
英文原题：The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma.
查看英文原题
The effects of HIV and oncogenic human papillomavirus on the tumor immune microenvironment of penile squamous cell carcinoma.
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中文摘要
阴茎鳞状细胞癌（PSCC）在一些发展中国家比发达国家更常见。HIV和/或高危型人乳头瘤病毒（hrHPV）感染是阴茎癌发展的危险因素。PSCC的肿瘤微环境可能预测预后，并可能为免疫治疗的最佳靶点提供信息。
我们在组织学上评估了阴茎肿瘤的免疫微环境，并确定了HIV和/或hrHPV感染是否以及如何影响该肿瘤微环境。我们进行了一项前瞻性分析性横断面研究，其中对在赞比亚卢萨卡大学教学医院就诊的35名患者的阴茎癌肿瘤进行了组织学分期，并评估了肿瘤浸润免疫细胞的存在和免疫检查点的表达。采用免疫组织化学评估免疫检查点和浸润免疫细胞，同时采用多重实时聚合酶链反应进行hrHPV基因分型。所有参与者的中位年龄为55岁。约24%为晚期组织学分期，83%为HIV+，63%通过多重实时聚合酶链反应在其肿瘤中检测到hrHPV。PDL1表达在HIV-参与者中显著高于HIV+参与者（p = 0.02）。
具有多重hrHPV感染的肿瘤表达TIM3的细胞数量显著高于单一hrHPV感染者（p = 0.04）。高级别肿瘤与低级别肿瘤相比，FoxP3+细胞（p = 0.02）、CD68+细胞（p = 0.01）、CD163+细胞（p = 0.01）、LAG3+细胞（p = 0.01）、PD1+细胞（p = 0.01）和TIM3+细胞（p = 0.03）的浸润显著更高。表达PD1和LAG3的细胞之间存在显著的中度至强正相关（⍴ = 0.69；p = 0.0001），PD1 与 TIM3（⍴ = 0.49；p = 0.017）以及 TIM3 与 LAG3 PDL1（⍴ = 0.61；p = 0.001）。
总之，阴茎鳞状细胞癌的肿瘤微环境似乎同时受到 HIV 和 HPV 感染的影响。TIM3 似乎是伴有 hrHPV 感染的 PSCC 患者的一个潜在治疗靶点。
展开英文摘要原文
Penile squamous cell carcinoma (PSCC) occurs more frequently in some developing countries compared to developed countries. Infection with HIV and/or high-risk human papillomavirus (hrHPV) are risk factors for penile cancer development. The tumor microenvironment of PSCC may predict prognosis and may inform on the best targets for immunotherapy.
We evaluated the immune microenvironment of penile tumors histologically, and determined whether and/or how HIV and/or hrHPV infections affect this tumor microenvironment.
We conducted a prospective analytical cross-sectional study in which penile cancer tumors from 35 patients presenting at the University Teaching Hospital in Lusaka, Zambia were histologically staged and assessed for presence of tumor infiltrating immune cells and expression of immune checkpoints. Immunohistochemistry was used to evaluate immune checkpoints and infiltrating immune cells, while multiplex real-time polymerase chain reaction was used for hrHPV genotyping. The median age of all participants was 55 years. About 24% had advanced histological stage, 83% were HIV+, and 63% had hrHPV detected in their tumors using multiplex real-time polymerase chain reaction.
PDL1 expression was significantly higher in HIV- participants than HIV+ participants (p = 0. 02). Tumors with multiple hrHPV infections had a significantly higher number of cells expressing TIM3 than those with one hrHPV (p = 0. 04). High grade tumors had a significantly higher infiltrate of FoxP3+ cells (p = 0. 02), CD68+ cells (p = 0.
01), CD163+ cells (p = 0. 01), LAG3+ cells (p = 0. 01), PD1+ cells (p = 0. 01) and TIM3+ cells (p = 0. 03) when compared with low grade tumours. There was significant moderate to strong positive correlation of cells expressing PD1 and LAG3 (⍴ = 0. 69; p = 0. 0001), PD1 and TIM3 (⍴ = 0. 49; p = 0. 017) and TIM3 and LAG3 PDL1 (⍴ = 0. 61; p = 0. 001).
In conclusion, the tumor microenvironment of penile squamous cell carcinoma seems to be affected by both HIV and HPV infections. TIM3 appears to be a potential therapeutic target in PSCC patients with hrHPV infections.
论文信息
- 作者
- Mumba C、Muhimbe Z、Mapulanga V、Kawimbe M、Mutale K、Hamasuku A、Musumali J、Mwale NK
- 第一作者单位
- Department of Pathology and Microbiology, School of Medicine, University of Zambia, Lusaka, Zambia.Zambia
- 通讯作者单位
- HHV8 Research Molecular Virology Laboratory, University Teaching Hospital, Lusaka, Zambia.Zambia
- 文献类型
- 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- PloS one2024
- 原文标识
- PubMed 38691575 · DOI 10.1371/journal.pone.0300729
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