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: Konstantinos Liapis, Andrew Clear, Andrew Owen, Rita Coutinho, Paul Greaves, Abigail M Lee, Silvia Montoto, Maria Calaminici, John G Gribben
• Journal: Blood (Blood) Vol. 122 Issue 3 Pg. 424-33 (Jul 18 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23652804 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Proto-Oncogene Proteins c-myc

Topics

• Acquired Immunodeficiency Syndrome (complications, pathology, virology)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Blood Vessels (pathology)
• Cellular Senescence (immunology)
• Epstein-Barr Virus Infections (complications, pathology)
• Female
• Gene Rearrangement (genetics)
• HIV-1 (physiology)
• Herpesvirus 4, Human (physiology)
• Humans
• Lymphocytes, Tumor-Infiltrating (pathology, virology)
• Lymphoma, AIDS-Related (drug therapy, pathology)
• Lymphoma, Large B-Cell, Diffuse (complications, drug therapy, pathology, virology)
• Macrophages (pathology)
• Male
• Middle Aged
• Neovascularization, Pathologic (complications, pathology)
• Proto-Oncogene Proteins c-myc (metabolism)
• Tumor Microenvironment
• Young Adult