Abstract
BACKGROUND: B7-H6 is a novel co-stimulatory protein exclusively expressed on a variety of cancer cells and associated with poor prognosis. T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive hematological malignancy whose treatment requires reliable prognostic biomarkers and therapeutic targets. However, the rare nature and delayed progression of T-LBL have limited its clinical management. METHODS: The expression of B7-H6 was analyzed by immunohistochemistry (IHC) in 65 T-LBL samples; the association with the clinicopathological characteristics and prognosis was also investigated. B7-H6-depleted Jurkat cells were also generated to investigate the effect of B7-H6 on cell proliferation, migration, and invasion. RNA sequencing was used to explore differentially expressed genes. RESULTS: B7-H6 was expressed in 61.5% (40/65) of T-LBL patients; of note, 38.5% (25/65) of patients showed membrane/cytoplasmic expression of B7-H6. Although the expression of B7-H6 varied across samples and did not correlate with patient survival, it was significantly associated with B symptoms, high ECOG scores (3 to 4), elevated serum lactate dehydrogenase level, and reduced complete remission at interim evaluation. B7-H6 underwent translocation into the nucleus of T-LBL cells, showing a specific nuclear localization sequence in the C-terminus. Moreover, the depletion of B7-H6 in Jurkat cells impaired cell proliferation, migration, and invasion. RNAseq showed the differential expression of RAG-1, which may be involved in the tumorigenesis of T-LBL. CONCLUSIONS: B7-H6 may serve as a novel prognostic biomarker and therapeutic target of T-LBL.