IL-10 induces the development of immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell non-Hodgkin lymphoma

Abstract

The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14+HLA-DRlow/− phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14+HLA-DRlow/− monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4+HLA-DRlow/− population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14+ monocytic cells with an HLA-DRlow/− phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14+HLA-DRlow/− population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14+HLA-DRlow/− population. Furthermore, we found that IL-10-induced CD14+HLA-DRlow/− monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14+HLA-DRlow/− monocytes in B-cell NHL.

The Possible Chemosensitizing Effect of Different Doses of Indol-3-Carbinol on Transplantable Tumor Model Treated with Doxorubicin

“…In the present study, implantation of ECC resulted in significant increase in tumor tissue TNF-α and IL-6 compared to the control group which was in the same line with other studies which reported that TNF-α and IL-6 have an important role in cancer development [22]. TNF-α and IL-6 are immunomodulatory cytokines that are frequently expressed in various types of cancer.…”

Monocytic myeloid-derived suppressor cells as a potent suppressor of tumor immunity in non-small cell lung cancer

“…The presence of IL-10 has been confirmed in various types of cancer, including B-cell non-Hodgkin lymphoma (NHL), prostate cancer, melanoma, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, multiple myeloma, glioblastoma and bladder carcinoma (5,(38)(39)(40). According to Feng et al (32), IL-10 is responsible for upregulating arginase 1 and therefore inhibits T-cell activation in patients with NSCLC.…”

“…According to Feng et al (32), IL-10 is responsible for upregulating arginase 1 and therefore inhibits T-cell activation in patients with NSCLC. Furthermore, Xiu et al (40) demonstrated that IL-10 is responsible for the development of Mo-MDSCs in B-cell NHL. Elevated production of IL-10 by macrophages associated with the tumor microenvironment correlates with poor prognosis, stage of disease, tumor size and lymph node metastasis (38,41).…”

Immunosuppressive CD14+HLA-DRlo/negmonocytes are elevated in pancreatic cancer and “primed” by tumor-derived exosomes

“…31 Cytokines that activate STAT3, such as IL-10, and IL-1b, have been implicated in the conversion of normal monocytes to immunosuppressive monocytes. 11,32,33 Interestingly, we conducted a 10-plex cytokine analysis on exosomes isolated from the plasma of healthy volunteers and normal pancreas cell lines compared to PC patient exosomes and cell lines. Preliminary results showed an increase in IL-1b in PC-Exo compared to the controls (data not shown).…”