Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1

Koya, Junji; Saito, Yuki; Kameda, Takuro; Kogure, Yasunori; Yuasa, Mitsuhiro; Nagasaki, Joji; McClure, Marni B.; Shingaki, Sumito; Tabata, Mariko; Tahira, Yuki; Akizuki, Keiichi; Kamiunten, Ayako; Sekine, Masaaki; Shide, Kotaro; Kubuki, Yoko; Hidaka, Tomonori; Kitanaka, Akira; Nakano, Nobuaki; Utsunomiya, Atae; Togashi, Yosuke; Ogawa, Seishi; Shimoda, Kazuya; Kataoka, Keisuke

doi:10.1158/2643-3230.bcd-21-0044

Cited by 12 publications

(35 citation statements)

References 34 publications

(50 reference statements)

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“…36 39 This study also verified that T-cell overexpression of PD-L1 can be transferred to surrounding lymphocytes and myeloid cells, thereby propagating PD-L1 upregulation and immune evasion. 39 Joo et al 40 further used scRNA-seq to analyze the clonality of CD4 + and CD8 + T cells in ATL, which revealed a prevalent Treg phenotype characterized by high expression of CCR4.…”

Section: Hpv-associated Cervical Cancers and Hnsccsupporting

confidence: 61%

Immune landscape of viral cancers: Insights from single‐cell sequencing

Lei

Wang

et al. 2022

Journal of Medical Virology

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Viral infections trigger a wide range of immune responses thought to drive tumorigenesis and malignant progression. Dissecting virus‐induced changes in the tumor immune microenvironment (TIME) is therefore crucial to identify key leukocyte populations that may represent novel targets for cancer therapy. Single‐cell sequencing approaches have now been widely applied to the analysis of various tumors, thus enabling multiomics characterization of the highly heterogeneous TIME that bulk‐sequencing cannot fully elucidate. In this review, we summarized key recent findings from sequencing studies of the immune infiltrate and antitumor response in virus‐associated cancers at single cell resolution. Additionally, we also reviewed recent developments in immunotherapy for virus‐associated cancers. We anticipate that the strategic use of single‐cell sequencing will advance our understanding of the TIME of viral cancers, leading to the development of more potent novel treatments.

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Section: Hpv-associated Cervical Cancers and Hnsccsupporting

confidence: 61%

Immune landscape of viral cancers: Insights from single‐cell sequencing

Lei

Wang

et al. 2022

Journal of Medical Virology

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“…Moreover, it is believed that ATL cells exhibit low viral protein expression along with genetic alteration and epigenetic silencing [ 69 ], which can potentially attenuate the effect of NIR-PIAS. Recently, single-cell analysis has indicated increased expression of cell surface proteins such as CD73 and CD99 in ATL cells [ 70 ]. These proteins may be novel therapeutic targets for ATL cells with defective proviruses devoid of Env expression.…”

Section: Discussionmentioning

confidence: 99%

Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy

Hatayama

Yamaoka

Morita

et al. 2022

Viruses

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Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, causes adult T-cell leukemia-lymphoma, HTLV-1 associated myelopathy/tropical spastic paraparesis, and HTLV-1 uveitis. Currently, no antiretroviral therapies or vaccines are available for HTLV-1 infection. This study aimed to develop an antibody against the HTLV-1 envelope protein (Env) and apply it to a near-infrared photoimmuno-antimicrobial strategy (NIR-PIAS) to eliminate HTLV-1 infected cells. We established mouse monoclonal antibodies (mAbs) against HTLV-1 Env by immunization with a complex of liposome and the recombinant protein. Detailed epitope mapping revealed that one of the mAbs bound to the proline-rich region of gp46 and exhibited no obvious neutralizing activity to inhibit viral infection. Instead, the mAb was rarely internalized intracellularly and remained on the cell surface of HTLV-1-infected cells. The antibody conjugated to the photosensitive dye IRDye700Dx recognized HTLV-1 infected cells and killed them following NIR irradiation. These results suggest that the novel mAb and NIR-PIAS could be developed as a new targeted therapeutic tool against HTLV-1 infected cells.

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“…One plausible explanation is that Foxp3 + infected T cells can evade immune surveillance via the expression of immune checkpoint molecules such as CTLA-4, PD-1 and TIGIT and immunoregulatory cytokines including IL-35 and IL-10. The similarities and differences of immunosuppressive mechanism between Treg and HTLV-1-infected cells still require further understanding and further studies utilizing single-cell methods for precise immunophenotyping will provide more evidence on how HTLV-1 evade host immunity ( 78 , 79 ).…”

Section: Immune Escape Mechanisms Used By Htlv-1-infected Cells For P...mentioning

confidence: 99%

“…HTLV-1 is also known to modulate the expression of immune checkpoint molecules on the cell surface of infected cells for immune evasion. Several studies have shown that HTLV-1 infection upregulates both the expression of stimulatory and inhibitory immune checkpoint molecules and is further augmented by leukemic transformation and ATL progression ( 78 , 79 , 94 ). For instance, the viral protein Tax is involved in the overexpression of OX40 ( 95 , 96 ), a costimulatory molecule which promotes cellular proliferation, enhances cell survival and suppresses Treg activity ( 97 ).…”

Section: Malignant Transformation Of Infected Cells and Additional Me...mentioning

confidence: 99%

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HTLV-1 persistence and leukemogenesis: A game of hide-and-seek with the host immune system

et al. 2022

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Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus which mainly infects CD4+ T cells and causes adult T-cell leukemia/lymphoma (ATL), is primarily transmitted via direct cell-to-cell transmission. This feature generates a wide variety of infected clones in hosts, which are maintained via clonal proliferation, resulting in the persistence and survival of the virus. The maintenance of the pool of infected cells is achieved by sculpting the immunophenotype of infected cells and modulating host immune responses to avoid immune surveillance. Here, we review the processes undertaken by HTLV-1 to modulate and subvert host immune responses which contributes to viral persistence and development of ATL.

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Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1

Abstract: High-dimensional single-cell landscape of immune alterations during HTLV-1 infection and leukemogenesis identifies hallmarks of premalignant and malignant T-cell states and the accompanying shift of systemic immune state toward myeloid and immunosuppressive.

Cited by 12 publications

References 34 publications

Immune landscape of viral cancers: Insights from single‐cell sequencing

Immune landscape of viral cancers: Insights from single‐cell sequencing

Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy

HTLV-1 persistence and leukemogenesis: A game of hide-and-seek with the host immune system

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