Journal article
Population analysis and immunologic landscape of melanoma in people living with HIV
Clinical cancer research, v 32(5)
08 Jan 2026
PMID: 41504629
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To dissect the clinical and immunological features of people living with HIV (PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer.
We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n=11), with downstream validation using multiplex immunofluorescence (n=15 PLWH, n=14 PLw/oH).
PLWH were diagnosed at a younger age, had greater representation of Hispanic and Black individuals, and showed reduced survival. They also had a markedly increased risk of brain metastases. PLWH experienced significant delays in initiating immune checkpoint inhibitor (ICI) therapy and had worse post-ICI survival, even after balancing covariates. Spatial transcriptomics revealed a more immunosuppressive tumor microenvironment in PLWH, with increased transcription of immune checkpoints (PD1, LAG3) and reduced antigen-presentation markers (HLA-DRB, B2M), with distinct spatial distributions in tumors and surrounding microenvironments. Multiplex immunofluorescence demonstrated features of an exhausted CD8⁺ T cell compartment, including enrichment of PD1intLAG3⁻ and PD1intLAG3⁺ subpopulations, and a significant accumulation of myeloid-derived suppressor cells (CD11b⁺ HLA-DR⁻ CD33⁺).
Melanoma in PLWH is associated with distinct clinical and immunological features, including delayed ICI treatment, reduced survival, and an immunosuppressive microenvironment with exhausted CD8⁺ T cells and expanded myeloid-derived suppressor cells. These findings suggest that chronic HIV infection may impair antitumor immunity in melanoma. Targeting the pathways identified here may improve therapeutic responses and outcomes in this population.
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Details
- Title
- Population analysis and immunologic landscape of melanoma in people living with HIV
- Creators
- Lindsay N Barger - Drexel UniversityDerek Wang - Rutgers, The State University of New JerseyAshley L Saravia - Drexel UniversityValeria Mezzano - NYU Langone HealthGyles Ward - NYU Langone HealthCynthia Loomis - NYU Langone HealthCarly Feldman - Thomas Jefferson University HospitalMadalina Tuluc - Thomas Jefferson UniversityRino S Seedor - Thomas Jefferson University HospitalPeter J Gaskill - Drexel UniversityAnna E Coghill - Moffitt Cancer CenterGita Suneja - Duke University Health SystemIman Dehzangi - Rutgers, The State University of New JerseyJennifer L Hope - Drexel UniversityGeorge Jour - New York UniversityGabriele Romano (Corresponding Author) - Drexel University
- Publication Details
- Clinical cancer research, v 32(5)
- Publisher
- American Association of Cancer Research
- Number of pages
- 12
- Grant note
- National Institute of Mental Health (NIMH): P30MH092177 National Cancer Institute (NCI): P30CA016087, S10-OD021747 National Institute on Drug Abuse (NIDA): DA057337, DA058051 W. W. Smith Charitable Trust (WWSCT): C2303 Congressionally Directed Medical Research Programs (CDMRP): ME220048 American Cancer Society (ACS): DBG-23-1036360-01 Sidney Kimmel Medical College, Thomas Jefferson University (SKMC): 901333, 00023568
We thank the AIDS and Cancer Specimen Resource (ACSR) for providing tumor samples from PLWH; ACSR is funded by the NCI. G. Romano is supported by the WW Smith Charitable Trust - Medical Research Program (#C2303); Department of Defense - Congressionally Directed Medical Research Programs, Melanoma Research Program (ME220048); American Cancer Society (DBG-23-1036360-01); Comprehensive NeuroHIV Center Developmental Research and Mentoring Core [National Institute of Mental Health (NIMH) - P30MH092177]; and Sidney Kimmel Comprehensive Cancer Center (#00023568 and #901333). L.N. Barger is supported by the Translational Research Training Grant in NeuroHIV (NIMH, T32-MH079785). P.J. Gaskill is supported by the National Institute of Drug Abuse, DA057337 and DA058051. The Experimental Pathology Research Laboratory (RRID: SCR_017928) is partially supported by the Cancer Center Support Grant (P30CA016087). The original Akoya/PerkinElmer Vectra multispectral imaging system was awarded through the Shared Instrumentation Grant S10 OD021747.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Pharmacology and Physiology
- Web of Science ID
- WOS:001704227300010
- Scopus ID
- 2-s2.0-105031818369
- Other Identifier
- 991022152238304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology