Indolent B-cell splenic lymphomas have T cells with an exhausted phenotype

Abstract

T cell dysregulation has been observed in many tumors, but has not been well-characterized in rare B-cell splenic lymphomas. We began defining the T cell populations in the tumor microenvironments of four human indolent B cell splenic lymphomas: splenic marginal zone lymphoma (SMZL), hairy cell leukemia (HCL), hairy cell leukemia variant (HCLv), and splenic diffuse red pulp small B-cell lymphoma (SDRPL). After Institutional Research Subjects Review Board approval, we studied de-identified cryopreserved bulk splenic tumor suspension cell isolates from fresh (less than 4 h) splenectomy tissue and matched intact formalin-fixed paraffin embedded (FFPE) tissue sections from 17 splenic lymphoma patients and 4 trauma patients (controls). Initial immunohistochemical staining analysis of FFPE tissue sections suggests that the distribution of intratumoral T cells is markedly different among B cell splenic lymphomas. In HCL, residual T cell zones appear retained, albeit diminished, while HCLv and SDRPL have markedly reduced T cells throughout with non-distinct zonation, and SMZL has prominent peritumoral collections of T cells at the interface of the neoplastic white pulp. High-parameter (32-color) fluorescence spectral flow cytometry (Cytek Aurora) analysis suggests that splenic lymphomas exhibit CD4+ and CD8+ T cells with higher proportions of transitional memory, regulatory, and exhausted phenotypes than controls. T cell activation may be enhanced in HCLv. HCLv and SMZL may have decreased naïve T cells. Finally, splenic lymphomas had higher proportions of T cells with an exhausted phenotype compared to trauma samples. In summary, our data suggests T cells are dysregulated in B-cell splenic lymphomas. American Association of Immunologists, Hairy Cell Leukemia Foundation / Sass Foundation for Medical Research, and generous donations by Elizabeth Aaron.