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1. State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI.

Author

Engels, Eric, Shiels, Meredith, Barnabas, Ruanne, Bohlius, Julia, Brennan, Paul, Castilho, Jessica, Chanock, Stephen, Clarke, Megan, Coghill, Anna, Combes, Jean-Damien, Dryden-Peterson, Scott, DSouza, Gypsyamber, Gopal, Satish, Jaquet, Antoine, Lurain, Kathryn, Makinson, Alain, Martin, Jeffrey, Muchengeti, Mazvita, Newton, Robert, Okuku, Fred, Orem, Jackson, Palefsky, Joel, Ramaswami, Ramya, Robbins, Hilary, Sigel, Keith, Silver, Sylvia, Suneja, Gita, Yarchoan, Robert, and Clifford, Gary

Subjects
cancer, epidemiology, human immunodeficiency virus, people living with HIV, prevention, United States, Humans, HIV, National Cancer Institute (U.S.), Neoplasms, HIV Infections, Anti-HIV Agents
Abstract

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

Published
2024

5. Transcriptional landscape of Kaposi sarcoma tumors identifies unique immunologic signatures and key determinants of angiogenesis

Author

Ramaswami, Ramya, Tagawa, Takanobu, Mahesh, Guruswamy, Serquina, Anna, Koparde, Vishal, Lurain, Kathryn, Dremel, Sarah, Li, Xiaofan, Mungale, Ameera, Beran, Alex, Ohler, Zoe Weaver, Bassel, Laura, Warner, Andrew, Mangusan, Ralph, Widell, Anaida, Ekwede, Irene, Krug, Laurie T., Uldrick, Thomas S., Yarchoan, Robert, and Ziegelbauer, Joseph M.

Published
2023
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7. Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy

Author

Uldrick, Thomas S, Adams, Scott V, Fromentin, Remi, Roche, Michael, Fling, Steven P, Gonçalves, Priscila H, Lurain, Kathryn, Ramaswami, Ramya, Wang, Chia-Ching Jackie, Gorelick, Robert J, Welker, Jorden L, O'Donoghue, Liz, Choudhary, Harleen, Lifson, Jeffrey D, Rasmussen, Thomas A, Rhodes, Ajantha, Tumpach, Carolin, Yarchoan, Robert, Maldarelli, Frank, Cheever, Martin A, Sékaly, Rafick, Chomont, Nicolas, Deeks, Steven G, and Lewin, Sharon R

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Genetics, Cancer, HIV/AIDS, 2.2 Factors relating to the physical environment, Aetiology, Infection, Antibodies, Monoclonal, Humanized, CD4-Positive T-Lymphocytes, HIV Infections, HIV-1, Humans, Neoplasms, Phylogeny, Programmed Cell Death 1 Receptor, RNA, Virus Latency, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART. Given that programmed cell death protein 1 (PD-1) expressing CD4+ T cells are preferentially infected with HIV in PLWH on ART, we aimed to determine whether administration of antibodies targeting PD-1 would reverse HIV latency in vivo. We therefore evaluated the impact of intravenous administration of pembrolizumab every 3 weeks on HIV latency in 32 PLWH and cancer on ART. After the first infusion of anti-PD-1, we observed a median 1.32-fold increase in unspliced HIV RNA and 1.61-fold increase in unspliced RNA:DNA ratio in sorted blood CD4+ T cells compared to baseline. We also observed a 1.65-fold increase in plasma HIV RNA. The frequency of CD4+ T cells with inducible virus evaluated using the tat/rev limiting dilution assay was higher after 6 cycles compared to baseline. Phylogenetic analyses of HIV env sequences in a participant who developed low concentrations of HIV viremia after 6 cycles of pembrolizumab did not demonstrate clonal expansion of HIV-infected cells. These data are consistent with anti-PD-1 being able to reverse HIV latency in vivo and support the rationale for combining anti-PD-1 with other interventions to reduce the HIV reservoir.

Published
2022

8. Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes.

Author

Gagliardi, Alessia, Porter, Vanessa L, Zong, Zusheng, Bowlby, Reanne, Titmuss, Emma, Namirembe, Constance, Griner, Nicholas B, Petrello, Hilary, Bowen, Jay, Chan, Simon K, Culibrk, Luka, Darragh, Teresa M, Stoler, Mark H, Wright, Thomas C, Gesuwan, Patee, Dyer, Maureen A, Ma, Yussanne, Mungall, Karen L, Jones, Steven JM, Nakisige, Carolyn, Novik, Karen, Orem, Jackson, Origa, Martin, Gastier-Foster, Julie M, Yarchoan, Robert, Casper, Corey, Mills, Gordon B, Rader, Janet S, Ojesina, Akinyemi I, Gerhard, Daniela S, Mungall, Andrew J, and Marra, Marco A

Subjects
Humans, Papillomaviridae, Papillomavirus Infections, Signal Transduction, DNA Methylation, Up-Regulation, Adult, Aged, Middle Aged, Uganda, Uterine Cervical Neoplasms, Female, Promoter Regions, Genetic, Transcriptome, Epigenome, Promoter Regions, Genetic, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV+) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV+, and performed extended mutation analysis on an additional 89 tumors. We detected human papillomavirus (HPV)-clade-specific differences in tumor DNA methylation, promoter- and enhancer-associated histone marks, gene expression and pathway dysregulation. Changes in histone modification at HPV integration events were correlated with upregulation of nearby genes and endogenous retroviruses.

Published
2020

9. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma

Author

Thomas, Nicole, Dreval, Kostiantyn, Gerhard, Daniela S., Hilton, Laura K., Abramson, Jeremy S., Ambinder, Richard F., Barta, Stefan, Bartlett, Nancy L., Bethony, Jeffrey, Bhatia, Kishor, Bowen, Jay, Bryan, Anthony C., Cesarman, Ethel, Casper, Corey, Chadburn, Amy, Cruz, Manuela, Dittmer, Dirk P., Dyer, Maureen A., Farinha, Pedro, Gastier-Foster, Julie M., Gerrie, Alina S., Grande, Bruno M., Greiner, Timothy, Griner, Nicholas B., Gross, Thomas G., Harris, Nancy L., Irvin, John D., Jaffe, Elaine S., Henry, David, Huppi, Rebecca, Leal, Fabio E., Lee, Michael S., Martin, Jean Paul, Martin, Marie-Reine, Mbulaiteye, Sam M., Mitsuyasu, Ronald, Morris, Vivian, Mullighan, Charles G., Mungall, Andrew J., Mungall, Karen, Mutyaba, Innocent, Nokta, Mostafa, Namirembe, Constance, Noy, Ariela, Ogwang, Martin D., Omoding, Abraham, Orem, Jackson, Ott, German, Petrello, Hilary, Pittaluga, Stefania, Phelan, James D., Ramos, Juan Carlos, Ratner, Lee, Reynolds, Steven J., Rubinstein, Paul G., Sissolak, Gerhard, Slack, Graham, Soudi, Shaghayegh, Swerdlow, Steven H., Traverse-Glehen, Alexandra, Wilson, Wyndham H., Wong, Jasper, Yarchoan, Robert, ZenKlusen, Jean C., Marra, Marco A., Staudt, Louis M., Scott, David W., and Morin, Ryan D.

Published
2023
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13. Characteristics and outcomes of KSHV-associated multicentric Castleman disease with or without other KSHV diseases

Author

Ramaswami, Ramya, Lurain, Kathryn, Polizzotto, Mark N., Ekwede, Irene, Waldon, Kirsta, Steinberg, Seth M., Mangusan, Ralph, Widell, Anaida, Rupert, Adam, George, Jomy, Gonçalves, Priscila H., Marshall, Vickie A., Whitby, Denise, Wang, Hao-Wei, Pittaluga, Stefania, Jaffe, Elaine S., Little, Richard F., Uldrick, Thomas S., and Yarchoan, Robert

Published
2021
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14. Sequencing of Kaposi's Sarcoma Herpesvirus (KSHV) genomes from persons of diverse ethnicities and provenances with KSHV-associated diseases demonstrate multiple infections, novel polymorphisms, and low intra-host variance.

Author

Marshall, Vickie A., Cornejo Castro, Elena M., Goodman, Charles A., Labo, Nazzarena, Liu, Isabella, Fisher, Nicholas C., Moore, Kyle N., Nair, Ananthakrishnan, Immonen, Taina, Keele, Brandon F., Polizzotto, Mark N., Uldrick, Thomas S., Mu, Yunxiang, Saswat, Tanuja, Krug, Laurie T., McBride, Kevin M., Lurain, Kathryn, Ramaswami, Ramya, Yarchoan, Robert, and Whitby, Denise

Subjects
KAPOSI'S sarcoma, GENETIC polymorphisms, VIRAL genetics, MIXED infections, GENOMES
Abstract

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics. Author summary: The prevalence of KSHV infection, one of eight viruses associated with human cancer, differs geographically as does the incidence of Kaposi sarcoma and other KSHV-associated diseases. Distribution of KSHV subtypes, defined solely by the sequence of the K1 gene, also differs by region. One hundred and two near full-length KSHV genomes from people with associated diseases from a wide variety of countries were sequenced, substantially increasing the number and diversity of KSHV genomes publicly available, thereby allowing the analysis of variance across geographical regions, potential contributions of viral genetics to the risk of disease, and viral evolution. Our data demonstrate that viral recombination is common, as previously published, and that infections with multiple KSHV genomes may also be frequent, which has not been widely reported. We did not find evidence of an association between viral subtypes and disease nor indications that different sampling sites from the same individual, including tumor specimens, harbored substantially different KSHV genomes. Our data significantly inform the current efforts to study epidemiology and the prevention of KSHV infection, including vaccine development, as well as the pathogenesis of associated diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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16. A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

Author

Hattori, Shin-ichiro, Higashi-Kuwata, Nobuyo, Hayashi, Hironori, Allu, Srinivasa Rao, Raghavaiah, Jakka, Bulut, Haydar, Das, Debananda, Anson, Brandon J., Lendy, Emma K., Takamatsu, Yuki, Takamune, Nobutoki, Kishimoto, Naoki, Murayama, Kazutaka, Hasegawa, Kazuya, Li, Mi, Davis, David A., Kodama, Eiichi N., Yarchoan, Robert, Wlodawer, Alexander, Misumi, Shogo, Mesecar, Andrew D., Ghosh, Arun K., and Mitsuya, Hiroaki

Published
2021
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18. HIV-Associated Cancers

Author

Yarchoan, Robert, Uldrick, Thomas S., Polizzotto, Mark N., Hope, Thomas J., editor, Richman, Douglas D., editor, and Stevenson, Mario, editor

Published
2018
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20. Viral, immunologic, and clinical features of primary effusion lymphoma

Author

Lurain, Kathryn, Polizzotto, Mark N., Aleman, Karen, Bhutani, Manisha, Wyvill, Kathleen M., Gonçalves, Priscila H., Ramaswami, Ramya, Marshall, Vickie Ann, Miley, Wendell, Steinberg, Seth M., Little, Richard F., Wilson, Wyndham, Filie, Armando C., Pittaluga, Stefania, Jaffe, Elaine S., Whitby, Denise, Yarchoan, Robert, and Uldrick, Thomas S.

Published
2019
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21. State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI

Author

Engels, Eric A., primary, Shiels, Meredith S., additional, Barnabas, Ruanne V., additional, Bohlius, Julia, additional, Brennan, Paul, additional, Castilho, Jessica, additional, Chanock, Stephen J., additional, Clarke, Megan A., additional, Coghill, Anna E., additional, Combes, Jean‐Damien, additional, Dryden‐Peterson, Scott, additional, D'Souza, Gypsyamber, additional, Gopal, Satish, additional, Jaquet, Antoine, additional, Lurain, Kathryn, additional, Makinson, Alain, additional, Martin, Jeffrey, additional, Muchengeti, Mazvita, additional, Newton, Robert, additional, Okuku, Fred, additional, Orem, Jackson, additional, Palefsky, Joel M., additional, Ramaswami, Ramya, additional, Robbins, Hilary A., additional, Sigel, Keith, additional, Silver, Sylvia, additional, Suneja, Gita, additional, Yarchoan, Robert, additional, and Clifford, Gary M., additional

Published
2023
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25. Elevated IL-13 in effusions of patients with HIV and primary effusion lymphoma as compared with other KSHV-associated disorders

Author

Ramaswami, Ramya, Lurain, Kathryn, Marshall, Vickie Ann, Rupert, Adam, Labo, Nazzarena, Cornejo-Castro, Elena, Miley, Wendell, Wang, Hao-Wei, Widell, Anaida, Lindsley, Matthew, Yuan, Constance, Stetler-Stevenson, Maryalice, Filie, Armando C., Whitby, Denise, Ziegelbauer, Joseph, Uldrick, Thomas S., and Yarchoan, Robert

Published
2020
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26. Elevated IL-13 in effusions of patients with HIV and primary effusion lymphoma as compared with other Kaposi sarcoma herpesvirus-associated disorders

Author

Ramaswami, Ramya, Lurain, Kathryn, Marshall, Vickie Ann, Rupert, Adam, Labo, Nazzarena, Cornejo-Castro, Elena, Miley, Wendell, Wang, Hao-Wei, Widell, Anaida, Lindsley, Matthew, Yuan, Constance, Stetler-Stevenson, Maryalice, Filie, Armando C., Whitby, Denise, Ziegelbauer, Joseph M., Uldrick, Thomas S., and Yarchoan, Robert

Published
2021
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32. Supplementary Table 1 from A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Author

Ramaswami, Ramya, primary, Uldrick, Thomas S., primary, Polizzotto, Mark N., primary, Wyvill, Kathleen M., primary, Goncalves, Priscila, primary, Widell, Anaida, primary, Lurain, Kathryn, primary, Steinberg, Seth M., primary, Figg, William Douglas, primary, Tosato, Giovanna, primary, Whitby, Denise, primary, and Yarchoan, Robert, primary

Published
2023
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33. Supplementary Figure 2 from A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Author

Ramaswami, Ramya, primary, Uldrick, Thomas S., primary, Polizzotto, Mark N., primary, Wyvill, Kathleen M., primary, Goncalves, Priscila, primary, Widell, Anaida, primary, Lurain, Kathryn, primary, Steinberg, Seth M., primary, Figg, William Douglas, primary, Tosato, Giovanna, primary, Whitby, Denise, primary, and Yarchoan, Robert, primary

Published
2023
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34. Supplementary Figure from Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection

Author

Ramaswami, Ramya, primary, Polizzotto, Mark N., primary, Lurain, Kathryn, primary, Wyvill, Kathleen M., primary, Widell, Anaida, primary, George, Jomy, primary, Goncalves, Priscila, primary, Steinberg, Seth M., primary, Whitby, Denise, primary, Uldrick, Thomas S., primary, and Yarchoan, Robert, primary

Published
2023
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35. Supplementary Materials and Methods from Sorafenib Is an Inhibitor of UGT1A1 but Is Metabolized by UGT1A9: Implications of Genetic Variants on Pharmacokinetics and Hyperbilirubinemia

Author

Peer, Cody J., primary, Sissung, Tristan M., primary, Kim, AeRang, primary, Jain, Lokesh, primary, Woo, Sukyung, primary, Gardner, Erin R., primary, Kirkland, C. Tyler, primary, Troutman, Sarah M., primary, English, Bevin C., primary, Richardson, Emily D., primary, Federspiel, Joel, primary, Venzon, David, primary, Dahut, William, primary, Kohn, Elise, primary, Kummar, Shivaani, primary, Yarchoan, Robert, primary, Giaccone, Giuseppe, primary, Widemann, Brigitte, primary, and Figg, William D., primary

Published
2023
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36. Supplementary Table 2 from A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Author

Ramaswami, Ramya, primary, Uldrick, Thomas S., primary, Polizzotto, Mark N., primary, Wyvill, Kathleen M., primary, Goncalves, Priscila, primary, Widell, Anaida, primary, Lurain, Kathryn, primary, Steinberg, Seth M., primary, Figg, William Douglas, primary, Tosato, Giovanna, primary, Whitby, Denise, primary, and Yarchoan, Robert, primary

Published
2023
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37. Data from Sorafenib Is an Inhibitor of UGT1A1 but Is Metabolized by UGT1A9: Implications of Genetic Variants on Pharmacokinetics and Hyperbilirubinemia

Author

Peer, Cody J., primary, Sissung, Tristan M., primary, Kim, AeRang, primary, Jain, Lokesh, primary, Woo, Sukyung, primary, Gardner, Erin R., primary, Kirkland, C. Tyler, primary, Troutman, Sarah M., primary, English, Bevin C., primary, Richardson, Emily D., primary, Federspiel, Joel, primary, Venzon, David, primary, Dahut, William, primary, Kohn, Elise, primary, Kummar, Shivaani, primary, Yarchoan, Robert, primary, Giaccone, Giuseppe, primary, Widemann, Brigitte, primary, and Figg, William D., primary

Published
2023
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38. Supplementary Figure 1 from A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Author

Ramaswami, Ramya, primary, Uldrick, Thomas S., primary, Polizzotto, Mark N., primary, Wyvill, Kathleen M., primary, Goncalves, Priscila, primary, Widell, Anaida, primary, Lurain, Kathryn, primary, Steinberg, Seth M., primary, Figg, William Douglas, primary, Tosato, Giovanna, primary, Whitby, Denise, primary, and Yarchoan, Robert, primary

Published
2023
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39. Supplementary Table from Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection

Author

Ramaswami, Ramya, primary, Polizzotto, Mark N., primary, Lurain, Kathryn, primary, Wyvill, Kathleen M., primary, Widell, Anaida, primary, George, Jomy, primary, Goncalves, Priscila, primary, Steinberg, Seth M., primary, Whitby, Denise, primary, Uldrick, Thomas S., primary, and Yarchoan, Robert, primary

Published
2023
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40. Supplementary Figures 1-4, Table 1 from Sorafenib Is an Inhibitor of UGT1A1 but Is Metabolized by UGT1A9: Implications of Genetic Variants on Pharmacokinetics and Hyperbilirubinemia

Author

Peer, Cody J., primary, Sissung, Tristan M., primary, Kim, AeRang, primary, Jain, Lokesh, primary, Woo, Sukyung, primary, Gardner, Erin R., primary, Kirkland, C. Tyler, primary, Troutman, Sarah M., primary, English, Bevin C., primary, Richardson, Emily D., primary, Federspiel, Joel, primary, Venzon, David, primary, Dahut, William, primary, Kohn, Elise, primary, Kummar, Shivaani, primary, Yarchoan, Robert, primary, Giaccone, Giuseppe, primary, Widemann, Brigitte, primary, and Figg, William D., primary

Published
2023
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48. Kaposi sarcoma herpesvirus viral load as a biomarker for leptomeningeal involvement by primary effusion lymphoma

Author

Lurain, Kathryn, primary, Ramaswami, Ramya, additional, Marshall, Vickie, additional, Castro, Elena M. Cornejo, additional, Labo, Nazzarena, additional, Miley, Wendell, additional, Moore, Kyle, additional, Roshan, Romin, additional, Mangusan, Ralph, additional, Jaffe, Elaine S., additional, Pittaluga, Stefania, additional, Wang, Hao-Wei, additional, Roth, Mark, additional, Filie, Armando C., additional, Uldrick, Thomas S., additional, Whitby, Denise, additional, and Yarchoan, Robert, additional

Published
2022
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