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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MDPI AG
2025-07-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/32/7/389 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Davey M. Smith |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1a76713b4d7f486a80a94faa50adc044 |
| institution | Kabale University |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-1a76713b4d7f486a80a94faa50adc0442025-08-20T03:36:18ZengMDPI AGCurrent Oncology1198-00521718-77292025-07-0132738910.3390/curroncol32070389HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung CancerDavey M. Smith0Elizabeth F. Rowland1Sara Gianella2Sandip Pravin Patel3Stephanie Solso4Cheryl Dullano5Robert Deiss6Daria Wells7Caroline Ignacio8Gemma Caballero9Magali Porrachia10Collin Kieffer11Antoine Chaillon12Department of Medicine, University of California, San Diego, CA 92093, USADepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USALeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Medicine, University of California, San Diego, CA 92093, USADepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USADepartment of Medicine, University of California, San Diego, CA 92093, USAHealth 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.https://www.mdpi.com/1718-7729/32/7/389HIVlung cancerintegrationtumor microenvironmentclonal expansionPTEN |
| spellingShingle | 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 HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer Current Oncology HIV lung cancer integration tumor microenvironment clonal expansion PTEN |
| title | HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer |
| title_full | HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer |
| title_fullStr | HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer |
| title_full_unstemmed | HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer |
| title_short | HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer |
| title_sort | hiv integration into the pten gene and its tumor microenvironment implications for lung cancer |
| topic | HIV lung cancer integration tumor microenvironment clonal expansion PTEN |
| url | https://www.mdpi.com/1718-7729/32/7/389 |
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