An increased density of FOXP3 positive regulatory T-cells (Tregs) can predict a good prognosis in diffuse large B-cell lymphoma (DLBCL) and its germinal center B-cell and nongerminal center B-cell subtypes, found a new study published in the International Journal of Experimental Pathology. On the other hand, increased CD68-positive tumor-associated macrophages can predict poor prognosis in the nongerminal center B-cell subtype.

“Given the limited value of the standard therapies in several DLBCL patients, microenvironment-directed therapy may be suggested as a novel approach to attain a more immunogenic environment with better drug delivery and ultimately improve the patients’ response rates,” the researchers wrote. “FOXP3 and CD68 expression may help the development of individualized therapy, prognostic prediction and therapy stratification.”

Read more about the prognosis of DLBCL

The prognostic value of FOXP3-positive Tregs and tumor-associated macrophages in DLBCL is still controversial, the researchers noted.

Here, a team of researchers from Egypt analyzed the expression of FOXP3 and CD68 as surrogates for Tregs and tumor-associated macrophages in DLBCL and assessed the relationship between their expression and survival and response to therapy. 

The results showed that a high density of FOXP3-positive Tregs was associated with better clinicopathological parameters and better therapy response. There was, however, no significant association between the expression of CD68 and any of the clinicopathologic features that were studied.

However, when they specifically looked at different DLBCL subtypes, the researcher found a significant association between high CD68 expression and poor prognosis in nongerminal center B-cell DLBCL but no significant association between CD68 expression and clinicopathological parameters in germinal center B-cell DLBCL.

They concluded that increased CD68 positive tumor-associated macrophage density may be predictive of poor prognosis in nongerminal center B-cell DLBCL.

“Further molecular studies on [a] larger sample size of DLBCL subtypes are still required to confirm their role and identify their correlation with different molecules in the surrounding environment,” they added.


Ahmed AM, Abdel-Hakeem SS, Amine MAF, et al. High density of FOXP3 predicts better prognosis in germinal and non-germinal centre diffuse large B-cell lymphoma. Int J Exp Pathol. Published online March 28, 2023. doi:10.1111/iep.12477