Prognostic implications of tumor-infiltrating macrophages, M2 macrophages, regulatory T-cells, and indoleamine 2,3-dioxygenase-positive cells in primary diffuse large B-cell lymphoma of the central nervous system.

Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive disease with a poor prognosis. The status of the tumor immune microenvironment in CNS-DLBCL remains unclear. We investigated the prognostic implications of tumor-associated macrophages (TAMs), regulatory T-cells (Tregs), and indoleamine 2,3-dioxygenase (IDO) cells in primary CNS-DLBCL (n = 114) by immunohistochemical analysis. The numbers of tumor-infiltrating immune cells, including CD68 TAMs, CD163 or CD204 M2 macrophages, FOXP3 Tregs, and IDO cells were all significantly lower in CNS-DLBCL versus systemic DLBCL (n = 165; all P < 0.001), but with little difference in the ratio of CD163/CD68 or CD204/CD68 cells. An increase in CD68 cell numbers was significantly associated with prolonged progression-free survival (PFS) and overall survival in patients with CNS-DLBCL (P = 0.004 and 0.021, respectively). In contrast, an increase in CD204 cell numbers or a higher ratio of CD204/CD68 cells was related to a shorter PFS (P = 0.020 and 0.063, respectively). An increase in IDO cell numbers was associated with a significantly longer PFS (P = 0.019). In combination, the status of low IDO cell numbers combined with low CD68 cell numbers, high CD204 cell numbers, or a high CD204/CD68 cell ratio all predicted poor PFS in multivariate analyses. This study showed that an increase in CD204 cell numbers, suggestive of M2 macrophages, was associated with poor clinical outcome in CNS-DLBCL, whereas increased CD68 or IDO cell numbers were related to a favorable prognosis. The analysis of tumor-infiltrating immune cells could help in predicting the prognosis of CNS-DLBCL patients and determining therapeutic strategies targeting tumor microenvironment.