Lymphoma monocytes have decreased HLA-DR expression, and this phenotype is associated with more aggressive disease. (A) Whole blood was stained for monocyte markers, including CD14 and HLA-DR. Flow cytometric analysis of CD14⁺ monocyte population that is CD14⁺HLA-DR^low/− is shown for age-matched controls (n = 27) and lymphoma patients (n = 40). Representative contour plot for each group is shown above (top panel). Flow cytometry analysis of monocyte expression of TNF-αRII (CD120b) is shown in the bottom panel (control, n = 12; lymphoma, n = 24). Decreased TNF-αRII expression is associated with increased percentage of CD14⁺HLA-DR^low/− monocytes (inset). (B) Within the lymphoma population, those with disseminated disease (stages III or IV disease, n = 34) had a higher percentage of CD14⁺HLA-DR^low/− monocytes than those with limited disease (stages I or II, n = 6; top panel). Similarly, when lymphoma samples are grouped by disease type (bottom panel), DLBCL (n = 18) had a significantly higher percentage of CD14⁺HLA-DR^low/− monocytes than the indolent histology group (4 mantle cell, 2 small lymphocytic lymphoma, one mucosa-associated lymphoid tissue, and one lymphoplasmacytoid). (C) The rate of progression for each patient is characterized by the average number of months per relapse, calculated by total number of months from initial diagnosis to time of sampling divided by total number of relapse. Distribution of percentage of CD14⁺HLA-DR^low/− monocytes is shown for each group as indicated (number of months per relapse: < 12, n = 4; 12-60, n = 28; > 60, n = 4). (D) Overall survival of lymphoma patients is shown. Black line represents patients whose monocytes had normal HLA-DR expression (n = 11; CD14⁺HLA-DR^low/− < 10% of CD14⁺ monocytes); and gray line, patients whose monocytes had loss of HLA-DR expression (n = 29; CD14⁺HLA-DR^low/− monocytes; monocytes where > 10% of CD14⁺ monocytes had lost HLA-DR expression).