Expression of CD68+ tumor‐associated macrophages in patients with diffuse large B‐cell lymphoma and its relation to prognosis

Abstract

Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies have shown that the presence of a high number of TAM is related to poor prognosis, suggesting that TAM predominantly exert pro-tumoral activity. The prognostic role of TAM in patients with diffuse large B-cell lymphoma (DLBCL), however, is so far unknown. Therefore, TAM were immunohistochemically stained with a CD68 antibody in a retrospective, population-based study including 176 DLBCL patients treated with curative intent. With the exception that patients >60 years of age had a larger number of CD68+ cells (1143 vs 1018 cells/mm2; P = 0.05), no significant differences were found between the number of CD68+ cells and other clinical factors. Similarly, germinal center B-cell (GCB)/non-GCB immunophenotype or low/high Ki-67 percentage were not associated with CD68 expression. Finally, no significant correlation was found between the number of CD68+ cells and progression-free survival (P = 0.34) or overall survival (P = 0.94). These data indicate that the pro-tumor effect of TAM has limited clinical relevance in DLBCL patients, which could imply that therapeutic strategies aimed at enhancing their anti-tumor activity are of continuous clinical interest.

Tumor-associated macrophages in diffuse large B-cell lymphoma

“…Whereas Nam et al 8 reported similar findings, as mentioned above, and the study by Cai et al 15 also showed that CD68 is a marker of poor outcome in CHOP-treated DLBCL patients, the studies by Hasselblom et al, 16 Meyer et al 17 and Coutinho et al 18 did not reveal significant associations between CD68 protein expression and survival. Furthermore, Wada et al 19 and Marchesi et al 20 reported that an M2 macrophage phenotype, as defined by double staining for CD68 and CD163, is associated with adverse outcome in R-CHOP-treated patients, whereas an M1 phenotype is not.…”

Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA-DRlow/negmonocytes mediates chemotherapy resistance

“…For example, while the gene signature of non-malignant cells in DLBCL indicates that a myeloidrich signature is a positive prognostic factor, 27 the total number of intra-tumor macrophages did not correlate with prognosis. 28 However, evaluation of macrophage phenotype indicated that M2 (CD163C) macrophage predict worse prognosis. 29 These studies highlight the heterogeneity of myeloid cell functions.…”

Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP

“…[7][8][9][10][11][12][13] IHC can be extended to clinical practice, which makes it highly attractive as a diagnostic and prognostic tool. Nevertheless, the results published regarding the immune microenvironment in DLBCL are contradictory.…”