Tumour‐immune microenvironment in duodenal‐type follicular lymphoma
Hiroaki Inoue, Shinya Rai, Hirokazu Tanaka, J. Luis Espinoza, Yosaku Watatani, Takahiro Kumode, Kentaro Serizawa, Shoko Nakayama, Yasuhiro Taniguchi, Yasuyoshi Morita, Yoichi Tatsumi, Takashi Ashida, Itaru Matsumura
Abstract
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.