B7-H6 Is Associated with Poor Prognosis and a Potential Therapeutic Target of T-Lymphoblastic Lymphoma

Background:B7-H6 is a novel co-stimulatory protein that is 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. The rare nature and delayed progression of T-LBL has limited its clinical management.

Methods:B7-H6 expression was analyzed by immunohistochemistry (IHC) in 65 T-LBL samples, and its association with clinicopathological characteristics and prognosis was analyzed. Jurkat cell with B7-H6 depletion was constructed to investigate the impact of B7-H6 on cell proliferation, migration, and invasion ability. RNA sequencing was used to explore aberrantly expressing genes.

Results:In this study, we used immunohistochemistry to show the expression of B7-H6 in 61.5% (40/65) of the cohort, including 38.5% (25/65) patients with membrane/cytoplasmic expression of B7-H6. Although B7-H6 expression varied across samples and did not correlate with patient survival, it was significantly associated with B symptoms, higher ECOG score (3-4), elevated serum lactate dehydrogenase, and reduced complete remission at interim evaluation. B7-H6 underwent translocation into the nucleus of T-LBL cells and had a specific nuclear localization sequence in the C-terminus. Depleting Jurkat cells of B7-H6 impaired cell proliferation, migration, and invasion. RNAseq showed the differential expression of RAG-1 that could be involved in the tumorigenesis of T-LBL.

Conclusions:B7-H6 may serve as a novel prognostic biomarker and therapeutic target of T-LBL.