title: The microenvironment of AIDS-related diffuse large B-cell lymphoma provides insight into the pathophysiology and indicates possible therapeutic strategies.
abstract: Despite the use of highly active antiretroviral therapy (HAART), AIDS-related lymphoma remains common. We investigated the tumor, microenvironment, and viral components in 41 AIDS-related diffuse large B-cell lymphomas (AR-DLBCLs) in the pre- and post-HAART era. The outcome has improved and the frequency of the prognostically unfavorable immunoblastic histology has decreased after HAART. Compared with sporadic cases, AR-DLBCL demonstrated increased hyperproliferation (P < .001) and c-Myc rearrangements, reduced CD4(+) (P < .001) and FOXP3(+) T cells (P < .001), increased activated cytotoxic cells (P < .001), but no difference in tumor-associated macrophages. Our analysis showed that AR-DLBCL is highly angiogenic with higher blood-vessel density than sporadic cases (P < .001) and highlighted the role of Epstein-Barr virus in angiogenesis. We recognized viral profiles and as a second step examined the reactive cytotoxic cell infiltrates. Our observation of markedly higher numbers of cytotoxic cells in AR-DLBCL with LMP1 and/or p24 compared with cases lacking viral antigens (P < .001) has important clinical implications, implicitly linked to the immunosurveillance theory. Whereas early initiation of HAART should improve immunosurveillance and reduce the incidence of LMP1-positive AR-DLBCL, cases without viral antigens appear able to avoid immunologic reaction and likely require additional strategies to improve surveillance.
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors: Konstantinos
authors: K
authors: Liapis
authors: Andrew
authors: A
authors: Clear
authors: Andrew
authors: A
authors: Owen
authors: Rita
authors: R
authors: Coutinho
authors: Paul
authors: P
authors: Greaves
authors: Abigail M
authors: AM
authors: Lee
authors: Silvia
authors: S
authors: Montoto
authors: Maria
authors: M
authors: Calaminici
authors: John G
authors: JG
authors: Gribben
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000473:pathology* / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D016922:Cellular Senescence / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D015497:HIV-1 / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology / Q000821:virology; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016271:Proto-Oncogene Proteins c-myc
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