Tumour-immune microenvironment in duodenal-type follicular lymphoma

Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8⁺ tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm² ) than in LSFL (1,150/mm² ) and ASFL (1,188/mm² ) (P = 0·002, P = 0·002, respectively). In addition, CD8⁺ PD1^-  T cells with non-exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer-lasting T cell-mediated immune response. Moreover, whereas FOXP3⁺ CTLA-4⁺ effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm² ), they were more abundant in LSFL (78/mm² ) and ASFL (109/mm² ) (P = 2·80 × 10^-5 , P = 4·74 × 10^-8 , respectively), and the numbers of eTregs correlated inversely with those of CD8⁺ TILs (r = -0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3^hi CD45RA^- CD25^hi eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10^-7 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL.