Abstract
Tumor-associated macrophages (TAMs) and regulatory T-cells (Tregs) play an important role in the tumor microenvironment. Here, we investigated the prognostic implications of TAMs and Tregs in 165 diffuse large B-cell lymphomas (DLBCLs) using immunohistochemistry. Survival analysis was performed among 109 DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). An increase in CD68 (+) cells was related to improved overall survival (OS) (p = 0.033). By contrast, an increased number of CD163 (+) cells and a higher ratio of CD163/CD68 (+) cells were significantly associated with shorter OS (p = 0.041 and 0.003) and progression-free survival (PFS) (p < 0.001 and 0.002). Patients with increased Tregs tended to have a better prognosis. In multivariate analysis, an increased ratio of CD163/CD68 (+) cells was an independent predictor of shorter OS and PFS. These results suggest that M2 macrophages might have a lymphoma-promoting function in DLBCL and predict poor clinical outcome. Therapeutic approaches targeting M2 macrophages would be valuable for the management of DLBCL in the R era.
Keywords:
M2 macrophages; Tumor microenvironment; diffuse large B-cell lymphoma; regulatory T-cells; tumor-associated macrophages.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal, Murine-Derived / administration & dosage
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Cyclophosphamide / administration & dosage
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Disease-Free Survival
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Doxorubicin / administration & dosage
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Female
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Forkhead Transcription Factors / metabolism
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Humans
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Immunohistochemistry
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Lymphoma, Large B-Cell, Diffuse / drug therapy*
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Lymphoma, Large B-Cell, Diffuse / pathology
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Macrophages / drug effects*
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Macrophages / metabolism
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Macrophages / pathology
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Male
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Middle Aged
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Multivariate Analysis
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Prednisone / administration & dosage
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Prognosis
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Receptors, Cell Surface / metabolism
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Rituximab
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Scavenger Receptors, Class A / metabolism
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / pathology
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Treatment Outcome
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Vincristine / administration & dosage
Substances
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Antibodies, Monoclonal, Murine-Derived
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD163 antigen
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CD68 antigen, human
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FOXP3 protein, human
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Forkhead Transcription Factors
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MSR1 protein, human
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Receptors, Cell Surface
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Scavenger Receptors, Class A
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Rituximab
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Prednisone