HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer

HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer

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 neuro...

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Main Authors: Davey M. Smith, Elizabeth F. Rowland, Sara Gianella, Sandip Pravin Patel, Stephanie Solso, Cheryl Dullano, Robert Deiss, Daria Wells, Caroline Ignacio, Gemma Caballero, Magali Porrachia, Collin Kieffer, Antoine Chaillon
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Current Oncology
Subjects:
HIV
lung cancer
integration
tumor microenvironment
clonal expansion
PTEN
Online Access:https://www.mdpi.com/1718-7729/32/7/389
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Summary: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.
ISSN:1198-0052
1718-7729

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