Anti-HTLV-1 immunity combined with proviral load as predictive biomarkers for adult T-cell leukemia-lymphoma

被引：6

作者：

Yamada, Asami ^{[1
]}

Yasunaga, Jun-ichirou ^{[1
,13
]}

Liang, Lihan ^{[1
]}

Zhang, Wenyi ^{[1
]}

Sunagawa, Junya ^{[2
]}

Nakaoka, Shinji ^{[3
]}

Iwami, Shingo ^{[4
]}

Kogure, Yasunori ^{[5
]}

Ito, Yuta ^{[5
,6
]}

Kataoka, Keisuke ^{[5
,7
]}

Nakagawa, Masanori ^{[8
]}

Iwanaga, Masako ^{[9
]}

Utsunomiya, Atae ^{[10
]}

Koh, Ki-Ryang ^{[11
]}

Watanabe, Toshiki ^{[12
]}

Nosaka, Kisato ^{[1
]}

Matsuoka, Masao ^{[1
]}

机构：

[1] Kumamoto Univ, Fac Life Sci, Grad Sch Med Sci, Dept Hematol Rheumatol & Infect Dis, Kumamoto, Japan

[2] Hokkaido Univ, Grad Sch Life Sci, Sapporo, Japan

[3] Hokkaido Univ, Fac Adv Life Sci, Sapporo, Japan

[4] Nagoya Univ, Grad Sch Sci, Div Nat Sci, Nagoya, Japan

[5] Natl Canc Ctr, Div Mol Oncol, Tokyo, Japan

[6] Jikei Univ, Sch Med, Dept Internal Med, Div Clin Oncol & Hematol, Tokyo, Japan

[7] Keio Univ, Sch Med, Dept Med, Div Hematol, Tokyo, Japan

[8] Kyoto Prefectural Univ Med, Kyoto, Japan

[9] Nagasaki Univ, Grad Sch Biomed Sci, Dept Clin Epidemiol, Nagasaki, Japan

[10] Imamura Gen Hosp, Dept Hematol, Kagoshima, Japan

[11] West Japan Railway Co, Dept Hematol, Osaka Gen Hosp, Osaka, Japan

[12] St Marianna Univ, Grad Sch Med, Dept Pract Management Med Informat, Tokyo, Japan

[13] Kumamoto Univ, Fac Life Sci, Grad Sch Med Sci, Dept Hematol Rheumatol & Infect Dis, 1-1-1 Honjo,Chuo Ku, Kumamoto 8608556, Japan

来源：

CANCER SCIENCE | 2024年 / 115卷 / 01期

关键词：

ATL; gag; HAM/TSP; HTLV-1; tax; VIRUS TYPE-I; HTLV-I; GENE-EXPRESSION; CARRIERS; TAX; LYMPHOCYTES; ANTIBODY; PX; LEUKAEMIA/LYMPHOMA; PROLIFERATION;

D O I：

10.1111/cas.15997

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases.

引用

页码：310 / 320

页数：11

共 47 条

[1] 2010 Rheumatoid Arthritis Classification Criteria An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative [J].