Smith Davey M, Rowland Elizabeth F, Gianella Sara, Patel Sandip Pravin, Solso Stephanie, Dullano Cheryl, Deiss Robert, Wells Daria, Ignacio Caroline, Caballero Gemma, Porrachia Magali, Kieffer Collin, Chaillon Antoine
Department of Medicine, University of California, San Diego, CA 92093, USA.
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
Curr Oncol. 2025 Jul 4;32(7):389. doi: 10.3390/curroncol32070389.
Health outcomes for people with HIV (PWH) have improved significantly with combination antiretroviral therapy (ART), yet the risk of lung cancer remains elevated. While a single case cannot establish causality, we describe here an investigation of a 74-year-old male PWH with de novo high-grade neuroendocrine small cell lung carcinoma. To investigate the potential contribution of HIV to cancer development, we performed HIV integration site sequencing on blood, tumor, and non-tumor tissue samples from the patient. We analyzed integration site distribution, clonal expansion, and associated gene disruption. Phosphatase and Tensin Homolog (PTEN) expression was evaluated using immunofluorescence and microscopy. A total of 174 unique HIV integration sites were identified, with 29.9% (52/174) located in clonally expanded cells. The most frequent integration site in clonally expanded cells was within the PTEN gene, representing 4.2% to 16.7% of all HIV-infected cells across samples. PTEN expression was markedly reduced in tumor regions relative to non-tumor tissue. Areas positive for HIV p24 antigen showed minimal PTEN expression. These findings suggest that HIV integration into the PTEN gene, coupled with clonal expansion of HIV-infected cells, may impair anti-tumor immune responses and promote cancer progression in PWH.
接受联合抗逆转录病毒疗法（ART）后，艾滋病毒感染者（PWH）的健康状况有了显著改善，但肺癌风险仍然较高。虽然单个病例无法确定因果关系，但我们在此描述了对一名74岁新发高级别神经内分泌小细胞肺癌的男性PWH的调查。为了研究艾滋病毒对癌症发展的潜在影响，我们对该患者的血液、肿瘤和非肿瘤组织样本进行了艾滋病毒整合位点测序。我们分析了整合位点分布、克隆扩增和相关基因破坏情况。使用免疫荧光和显微镜评估磷酸酶和张力蛋白同源物（PTEN）的表达。共鉴定出174个独特的艾滋病毒整合位点，其中29.9%（52/174）位于克隆扩增细胞中。克隆扩增细胞中最常见的整合位点位于PTEN基因内，占所有样本中艾滋病毒感染细胞的4.2%至16.7%。与非肿瘤组织相比，肿瘤区域的PTEN表达明显降低。艾滋病毒p24抗原阳性区域的PTEN表达极少。这些发现表明，艾滋病毒整合到PTEN基因中，再加上艾滋病毒感染细胞的克隆扩增，可能会损害PWH的抗肿瘤免疫反应并促进癌症进展。
