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. 2020 Oct;191(2):243-252.
doi: 10.1111/bjh.16715. Epub 2020 May 8.

Tumour-immune microenvironment in duodenal-type follicular lymphoma

Hiroaki Inoue  1 , Shinya Rai  1 , Hirokazu Tanaka  1 , J Luis Espinoza  1 , Yosaku Watatani  1 , Takahiro Kumode  1 , Kentaro Serizawa  1 , Shoko Nakayama  1 , Yasuhiro Taniguchi  1 , Yasuyoshi Morita  1 , Yoichi Tatsumi  1 , Takashi Ashida  1 , Itaru Matsumura  1
Affiliations

Tumour-immune microenvironment in duodenal-type follicular lymphoma

Hiroaki Inoue et al. Br J Haematol. 2020 Oct.

Abstract

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 FOXP3hi CD45RA- CD25hi 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.

Keywords: duodenal-type Ffollicular lymphoma; effector regulatory T cell; follicular lymphoma; regulatory T cell; tumor immune microenvironment; tumor infiltrating T lymphocytes.

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