High levels of the transmembrane glycoprotein, triggering receptors expressed on myeloid cells 2 (TREM2) on the surface of circulating monocytic myeloid-derived suppressive cells in patients with diffuse large B-cell lymphoma (DLBCL) who have not been previously treated is a poor prognostic factor, according to a new study published in the journal Experimental Hematology & Oncology. This is the case for both progression-free and overall survival.
Surface-TREM2 could therefore potentially be a novel target for immunotherapy for DLBCL, the researchers noted.
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It was already known that circulating monocytic myeloid-derived suppressive cells are associated with poor prognosis in DLBCL. However, the role of TREM2 on their surface has not been investigated previously, they added.
In the present study, a team of researchers from Taiwan led by Nien-Jung Chen, PhD analyzed the expression of TREM2 on circulating monocytic myeloid-derived suppressive cells from patients with DLBCL as well as its clinical effect.
The team enrolled 100 patients with DLBCL who were newly diagnosed with DLBCL and had not yet received any treatment.
They reported that higher levels of monocytic myeloid-derived suppressive cells at the time of diagnosis were predictive of worse progression-free and overall survival, as expected.
The researchers also reported that patients with higher International Prognostic Index scores had significantly higher levels of TREM2 on the surface of their monocytic myeloid-derived suppressive cells. These patients also had more bone marrow involvement and lower absolute CD4+ or CD8+ T cell counts in peripheral blood.
The levels of TREM2 on circulating monocytic myeloid-derived suppressive cells could be grouped into 3 as low, medium, and high with low being less than 2 %, medium being between 2% and 44%, and high being more than 44%.
The researchers calculated that high levels of TREM2 were an independent prognostic factor for both progression-free and overall survival associated with worse survival.
The researchers also reported that TREM2 levels were negatively associated with absolute CD8+ T cell counts in peripheral blood and positively correlated with intracellular arginase 1 (Arg 1) levels within monocytic myeloid-derived suppressive cells.
Using a mouse model, the researchers also demonstrated that myeloid-derived suppressive cells in wild-type animals had significantly higher levels of Arg1 mRNA and could better suppress the proliferation of co-cultured CD8+ T cells compared to myeloid-derived suppressive cells obtained from animals in which the Trem 2 gene was knocked out. Finally, adding Arg1 inhibitors or supplementing L-arginine could reduce the suppressive ability of these cells.
More research is needed where surface TREM2 is targeted as a potential approach to treating DLBCL, the authors concluded.
Wang HY, Yang FC, Yang CF, et al. Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-naïve diffuse large B-cell lymphoma. Exp Hematol Oncol. Published online April 7, 2023. doi:10.1186/s40164-023-00399-x