サカモト　ユウマ   Yuma Sakamoto   坂本　祐真    所属   川崎医科大学  医学部 基礎医学　免疫学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Clinicopathological significance of CD28 overexpression in adult T-cell leukemia/lymphoma.
掲載誌名	正式名：Cancer science 略　 称：Cancer Sci ISSNコード：13497006/13479032
掲載区分	国外
巻・号・頁	113(1),pp.349-361
著者・共著者	Yuma Sakamoto, Takashi Ishida, Ayako Masaki, Morishige Takeshita, Hiromi Iwasaki, Kentaro Yonekura, Yukie Tashiro, Asahi Ito, Shigeru Kusumoto, Shinsuke Iida, Atae Utsunomiya, Ryuzo Ueda, Hiroshi Inagaki
発行年月	2022/01
概要	CD28, one of the costimulatory molecules, has a pivotal role in T-cell activation, and its expression is strictly regulated in normal T cells. Gain-of-function genetic alterations involving CD28 have been frequently observed in adult T-cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28 fusions and copy number variations, may not only confer continuous, prolonged, and enhanced CD28 signaling to downstream pathways but also induce overexpression of the CD28 protein. In this study, 120 ATLL cases were examined by immunohistochemistry for CD28 and its ligands CD80 and CD86, and their expression on tumor cells was semiquantitatively evaluated. CD28 was overexpressed in 55 (46%) cases, and CD80 or CD86 (CD80/CD86) was infrequently overexpressed in 12 (11%). Compared with non-overexpressers, CD28 overexpressers showed a higher frequency of CD28 genetic alterations and had an increased number of CD80/CD86-positive non-neoplastic cells infiltrating tumor microenvironment. In the entire ATLL patient cohort, CD28 overexpressers showed a significantly poorer overall survival (OS) compared with non-overexpressers (P = .001). The same was true for a subgroup who were treated with multidrug regimens with or without mogamulizumab. CD28 overexpression had no prognostic impact in the group who received allogeneic hematopoietic stem cell transplantation. In the multivariate analysis for OS, CD28 overexpression was selected as an independent risk factor. These results suggest ATLL patients with CD28 overexpression have more aggressive clinical course and are more refractory to treatment with multidrug chemotherapy. CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL patients, and further prospective studies are warranted to establish its prognostic significance.
DOI	10.1111/cas.15191
PMID	34738707