Tumour‐immune microenvironment in duodenal‐type follicular lymphoma

Summary 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/mm 2 ) than in LSFL (1,150/mm 2 ) and ASFL (1,188/mm 2 ) ( 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/mm 2 ), they were more abundant in LSFL (78/mm 2 ) and ASFL (109/mm 2 ) ( 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.