title: An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.
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.
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul , Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Nam
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Paik
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D000069283:Rituximab; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003520:Cyclophosphamide; D004317:Doxorubicin; D051858:Forkhead Transcription Factors; D011241:Prednisone; D011956:Receptors, Cell Surface; D000069283:Rituximab; D051117:Scavenger Receptors, Class A; D014750:Vincristine; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C418974:FOXP3 protein, human; C495139:MSR1 protein, human
keywords: M2 macrophages; Tumor microenvironment; diffuse large B-cell lymphoma; regulatory T-cells; tumor-associated macrophages