PDL1 expression is elevated prior to AIDS-related Non-Hodgkin’s lymphoma diagnosis

Abstract

Abstract The risk of developing non-Hodgkin’s lymphoma (NHL) is greatly elevated in HIV infection, and AIDS-associated NHL (AIDS-NHL) remains a significant problem, even in those receiving anti-retroviral therapy. AIDS-NHL is thought to develop due to: 1) loss of immunoregulation of Epstein-Barr virus infected cells and/or 2) the accrual of genetic errors associated with B-cell activation driven by HIV infection. A population of B cells that express PDL1, secrete CXCL13, IL6 and IL10, and can regulate T-cell function by interacting with PD1, has been recently described. We previously showed that serum levels of CXCL13, IL-16 and IL-10 are elevated prior to, as well as after, AIDS-NHL diagnosis. Also, others have described that PDL1 and PD1 expression are elevated in HIV infection, and that this has an impact on T-cell function. PDL1 expression on B cells may contribute to the development of AIDS-NHL in a dual fashion by: 1) enhancing B-cell activation, and 2) by impairing/inhibiting T-cell function through PD1:PDL1 interactions. Hence, we hypothesized that levels of CD19+PDL1+ cells may be elevated prior to AIDS-NHL diagnosis and may play a role in lymphomagenesis. To investigate this hypothesis, we conducted a nested case-control study within the Multicenter AIDS Cohort Study, obtaining viable frozen PBMC from HIV+ subjects who later developed NHL (cases, n=31) and from HIV+ subjects who did not develop NHL (HIV+ matched controls, n=29) and performed multi-color flow cytometry. We observed that the numbers of circulating CD19+PDL1+ cells in cases were elevated prior to AIDS-NHL diagnosis, when compared to HIV+ controls (p=0.026), suggesting that CD19+PDL1+ cells may be playing an important role in the development of AIDS-NHL.