PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

Kozako, Tomohiro; Yoshimitsu, Makoto; Fujiwara, Hiroshi; Masamoto, Izumi; Horai, Sawako; White, Yohann; Akimoto, Masaki; Suzuki, Susumu; Matsushita, Kakushi; Uozumi, Kimiharu; Tei, Chuwa; Arima, Naomichi

doi:10.1038/leu.2008.272

Cited by 163 publications

(139 citation statements)

References 44 publications

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“…Our findings contrast with what has been shown in HTLV-1 infection, where a marked increase of PD-1 expression could be found both in asymptomatic carriers and in patients with ATLL (43). Although these findings would not suggest immune exhaustion of virus-specific CTLs in HTLV-2 infection, this will require further studies.…”

Section: Figurecontrasting

confidence: 55%

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Oliveira

Hayakawa

Schor

et al. 2009

The Journal of Immunology

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Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11–19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8+ T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8+ T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2(11–19) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.

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Section: Figurecontrasting

confidence: 55%

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Oliveira

Hayakawa

Schor

et al. 2009

The Journal of Immunology

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“…Primary ATL cells in 21.7％ of ATL patients expressed PD-L1, while elevated expression was not observed in cells from ACs. 43) Finally, in functional studies we observed that an anti-PD-L1 antagonistic antibody upregulated HTLV-1-speciˆc CD8＋ T-cell response (Fig. 2B).…”

Section: Decreased Frequency and Function Of Htlv-1-specific Ctl In Atlmentioning

confidence: 97%

“…These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8＋ T-cell clones may be one of the risks of ATL development. 32,33) patients may be involved in progression from HTLV-1 carrier to ATL, and also contribute to the aggressiveness of this disease, which is refractory to treatment.…”

Section: Decreased Frequency and Function Of Htlv-1-specific Ctl In Atlmentioning

confidence: 99%

New Strategy of Adult T-cell Leukemia Treatment Targeted for Anti-tumor Immunity and a Longevity Gene-encoded Protein

Kozako

2011

YAKUGAKU ZASSHI

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Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm with a poor prognosis, developing after long-term infection with human T-cell leukemia virus-1 (HTLV-1). Multiple factors (e.g., virus, host cells, epigenetic aberrations, and immune factors) have been implicated in the development of ATL, although the underlying mechanisms of leukemogenesis have not been fully elucidated. Despite recent progress in both chemotherapy and supportive care for hematological malignancies, the prognosis of ATL is still poor; overall survival at 3 years is only 24 ％. New strategies for the therapy and prophylaxis of ATL (e.g., vaccines and novel molecular target agents) are still required. This article reviews new strategy of ATL treatment targeted for HTLV-1-speciˆc cytotoxic T-lymphocytes (CTLs) and SIRT1, a longevity gene-encoded protein. HTLV-1-speciˆc CTLs play a critical role in the host immune response against HTLV-1. We have described here the decreased frequency and function of HTLV-1-speciˆc CD8＋ T cells in ATL patients and the e‹cient induction of the HTLV-1-speciˆc CTLs response in human leukocyte antigen-A 0201-transgenic mice by the HTLV-1/hepatitis B core chimeric particle and oligomannose-coated liposomes encapsulating HTLV-1 epitope without adjuvant, suggesting that the e‹cient antigen delivery system and CTL induction can be exploited to develop a prophylactic vaccine model against tumors and infectious diseases. Furthermore, our studies suggest that SIRT1, a longevity gene-encoded protein, is a crucial anti-apoptotic molecule in ATL cells, and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL. These studies targeted for antitumor immunity such as vaccine and SIRT1 may support the new prophylactic and therapeutic approach for ATL.

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“…We have reported PD-1 expression on Tax-specific CTLs may indicate Tax-specific T cell exhaustion [51].…”

Section: Immunological Impairment Of Htlv-1 Specific T Cellsmentioning

confidence: 96%

Prevention of Human T-Cell Lymphotropic Virus Infection and Adult T-Cell Leukemia

Yoshimitsu¹,

Kozako²,

Arima³

2013

T-Cell Leukemia - Characteristics, Treatment and Prevention

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PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients

Cited by 163 publications

References 44 publications

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

New Strategy of Adult T-cell Leukemia Treatment Targeted for Anti-tumor Immunity and a Longevity Gene-encoded Protein

Prevention of Human T-Cell Lymphotropic Virus Infection and Adult T-Cell Leukemia

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