Lymphocyte-to-Monocyte Ratio May Serve as a Better Prognostic Indicator Than Tumor-associated Macrophages in DLBCL Treated with Rituximab

There are multiple prognostic indicators for diffuse large B-cell lymphoma (DLBCL) including the international prognostic index (IPI), and gene expression profiling (GEP) to classify the disease into germinal center B-cell and activated B-cell subtypes, the latter harboring inferior prognosis. More recently, tumor-associated macrophages (TAM) and lymphocyte-to-monocyte ratio (LMR) were found to have prognostic implications in DLBCL. However, consensus is yet to be reached in terms of the significance of each. In this study, we evaluated the prognostic value of TAM as assessed by CD163 or CD68 positivity by immunohistochemistry on tissue biopsies and LMR was calculated from peripheral blood differential, with focus on the inclusion of rituximab as a treatment modality. The number of CD68-positive cells in the tumor microenvironment did not exhibit significant prognostic value, whereas higher number of CD163-positive cells was associated with inferior overall survival in patients treated with chemotherapy alone. This effect was no longer evident in patients treated with rituximab containing chemoimmunotherapy. In contrast, the prognostic significance of LMR on survival was more persistent regardless of treatment. There was no association between LMR and the number of CD163-positive cells. Our results suggest that LMR is the more easily and widely available prognostic marker in this era of chemoimmunotherapy. Our finding supports previous literature that the effect of TAM can vary according to treatment. Interaction between rituximab and TAM warrant further scientific investigation for mechanistic insights into targeted therapeutics.