High prevalence of oral HPV and HHV8 infections was observed; MSM had the highest figures, despite better control of HIV infection.

The peculiar localization of body cavity lymphomas implies a specific contribution of the intracavitary microenvironment to the pathogenesis of these tumors. In this study, primary effusion lymphoma (PEL) was used as a model of body cavity lymphoma to investigate the role of mesothelial cells, which line the serous cavities, in lymphoma progression. The crosstalk between mesothelial and lymphomatous cells was studied in cocultures of primary human mesothelial cells (HMC) with PEL cells and a xenograft mouse model of peritoneal PEL. PEL cells were found to induce type 2 epithelial–mesenchymal transition (EMT) in HMC, which converted into a myofibroblastic phenotype characterized by loss of epithelial markers (pan cytokeratin and E-cadherin), expression of EMT-associated transcriptional repressors (Snail1, Slug, Zeb1, Sip1), and acquisition of α-smooth muscle actin (α-SMA), a mesenchymal protein. A progressive thickening of serosal membranes was observed in vivo, accompanied by loss of cytokeratin staining and appearance of α-SMA-expressing cells, confirming that fibrosis occurred during intracavitary PEL development. On the other hand, HMC were found to modulate PEL cell turnover in vitro, increasing their resistance to apoptosis and proliferation. This supportive activity on PEL cells was retained after transdifferentiation, and was impaired by interferon-α2b treatment. On the whole, our results indicate that PEL cells induce type 2 EMT in HMC, which support PEL cell growth and survival, providing a milieu favorable to lymphoma progression. Our findings provide new clues into the mechanisms involved in lymphoma progression and may indicate new targets for effective treatment of malignant effusions growing in body cavities.

LETTERS TO THE EDITOR© F e r r a t a S t o r t i F o u n d a t i o n

Human herpesvirus 8 is associated with the development of primary effusion lymphoma (PEL), an aggressive non-Hodgkin’s lymphoma characterized by the proliferation of the malignant lymphocytes almost exclusively in large serous cavities. The mechanisms involved in the preferential tropism for serous cavities and in the aggressive course of PEL remain to be fully clarified. To study the role of host microenvironment in PEL progression, we previously compared the antineoplastic activity of a murine interferon◊-expressing lentiviral vector (mIFN-◊-LV) to that of a human IFN-◊-LV in a murine model of peritoneal PEL. We demonstrated that in vivo targeting of the murine microenvironment showed an antineoplastic activity comparable to that observed with the hIFN-◊-LV. These findings highlighted the relevant role of body cavity environment in PEL growth and indicated that modulation of microenvironment may impair PEL growth in vivo. By using cocultures of PEL cell lines with human mesothelial cells (HMC), we mimicked the interactions existing in body cavities to analyze the mechanisms involved in PEL progression. PEL cells induced a myofibroblastic morphology in HMC, paralleled by an expression profile indicative of the occurrence of epithelial-mesenchymal transition (EMT). Moreover, HMC increased proliferation and resistance to apoptosis of PEL cells. These data indicate that PEL cells induce EMT in HMC and fibrosis of serous membranes. In turn, HMC modulate PEL cell turnover, thus providing a milieu favorable to PEL progression. These findings open new perspectives into the mechanisms involved in PEL progression and may indicate new targets for PEL treatment.