Tumour‐immune microenvironment in duodenal‐type follicular lymphoma

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 advancedstage 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 = 0Á002, P = 0Á002, respectively). In addition, CD8 + PD1 À 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 = 2Á80 9 10 À5 , P = 4Á74 9 10 À8 , respectively), and the numbers of eTregs correlated inversely with those of CD8 + TILs (r = À0267; P = 0Á018). Furthermore, DTFL showed significantly fewer circulating FOX-P3 hi CD45RA-CD25 hi eTregs (0Á146%) than ASFL (0Á497%) and healthy controls (0Á639%) (P = 0Á0003, P = 6Á79 9 10 À7 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL.

Decreased expression of T‐cell‐associated immune markers predicts poor prognosis in patients with follicular lymphoma

“…Several lines of evidence indicated that FL cells depend on the interactions with non‐malignant cells that constitute the TME for their growth and survival 1,42 . Particularly, because of the indolent feature of FL cells, the prognosis of FL is substantially affected by the TME, which consists of various types of T lymphocytes (CTLs, Tregs, and so on), B lymphocytes, and TAMs.…”

Clinicopathological factors and tumor microenvironment markers predicting watch‐and‐wait discontinuation in 82 patients with follicular lymphoma

“…In the present study, the correlation of duodenal‐type FL with a low number of interfollicular/intrafollicular CD4 + and FOXP3 + cells suggested that the immuno‐microenvironment might be responsible for the distinct clinical and biological features of duodenal‐type FL. Similarly, Inoue et al 30 reported that FOXP3 + CTLA‐4 + effector Tregs are rarely observed in the neoplastic follicles of duodenal‐type FL, whereas they are more abundant in nodal FL. Although duodenal‐type FL usually shows an indolent clinical course and many patients receive a WW strategy, patients with a WW score above 1 had some risks of WW discontinuation.…”

Duodenal Follicular Lymphoma: Track or Treat?

“…Moreover, we reviewed four retrospective papers reporting a DFL clinical series (Table 2) [23][24][25][26]. According to the literature, there are several therapeutic approaches, including "watch and wait," radiotherapy, rituximab-chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisone (R-CHOP), and rituximab alone [27].…”