ORCID Profile
0000-0002-9502-1781
Current Organisation
IRCCS, Centro di Riferimento Oncologico
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Publisher: Wiley
Date: 10-06-2008
DOI: 10.1002/IJC.23621
Abstract: Immunotherapy approaches targeting Epstein-Barr virus (EBV)-encoded antigens induce objective clinical responses only in a fraction of patients with undifferentiated nasopharyngeal carcinoma (UNPC). In the present study, we have characterized the immunogenicity of the EBV-encoded BARF1 oncogene with the aim to assess whether this protein could constitute a new target antigen for immunotherapy in this setting. Spontaneous CD4+ and CD8+ T cell responses specific for the recombinant p29 BARF1 protein were detected by IFNgamma-ELISPOT in both EBV-seropositive donors and UNPC patients, but not in EBV-seronegative in iduals. Using immunoinformatic prediction tools, we have selected 5 different candidate BARF1 T cell epitopes presented by HLA-A*0201. Although only one of these peptides was able to bind HLA-A2 with low affinity in the T2 stabilization assay, all 5 BARF1 nonamers readily elicited specific CD8+ T cell responses in EBV-seropositive HLA-A*0201+ donors and UNPC patients. Notably, the magnitude of CD8+ T cell responses to the whole BARF1 protein and derived A*0201 peptides was significantly higher in UNPC patients than in healthy donors. Moreover, cytotoxic T lymphocytes specific for the p2-10, p23-31, or p49-57 BARF1 peptides were easily obtained from HLA-A*0201+ donors. These cultures were not only able to lyse autologous targets loaded with the antigenic peptide, but also recognized tumor cells endogenously expressing BARF1 in an antigen-specific and HLA-A2-restricted manner. These findings, indicate that BARF1 is a particularly attractive antigen with immunogenic properties in most UNPC patients and provide valuable information to develop new strategies to improve the efficacy of EBV-targeting immunotherapy of UNPC patients.
Publisher: Springer Science and Business Media LLC
Date: 28-03-2019
Publisher: Proceedings of the National Academy of Sciences
Date: 02-11-2015
Abstract: Non-Hodgkin lymphomas (NHLs) are associated with HIV-1 infection, but the HIV1 genome is not detectable in malignant B cells. Here we show that variants of the HIV-1 matrix protein p17 (vp17s) are detected in the NHL specimens of HIV+ patients. These vp17s are more frequently detected in HIV+ patients with NHL than in patients without NHL. These vp17s display a potent B-cell growth-promoting activity, which is exerted by activating the Akt signaling pathway. Results obtained by CD spectroscopy and thermal denaturation suggest that mutation-induced protein destabilization may lead to a conformational change potentially responsible for the viral protein to promote B-cell growth. Our results suggest that vp17s may have a role in sustaining lymphomagenesis, thus offering new opportunities to prevent and/or treat HIV-associated NHLs.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2012
DOI: 10.1038/BJC.2012.2
Publisher: American Society of Hematology
Date: 10-09-2009
Publisher: Springer Science and Business Media LLC
Date: 06-02-2016
Publisher: Bentham Science Publishers Ltd.
Date: 31-10-2013
DOI: 10.2174/18715206113136660348
Abstract: Aging is a complex phenomenon involving multiple physiological functions. Among these, very important are the modifications induced in the immune system these modifications may be related to cancer development, a disease of older people. We herein describe the age-dependent alterations observed in the various arms of the immune system. Both innate and adaptive immunity are compromised during aging, a condition where an inflammatory status contributes to promote immune suppression and tumour growth. Collectively, aging of the immune system may produce detrimental consequences on the response against tumours in old patients. In fact, preclinical studies and clinical observations in humans have demonstrated age-associated alterations in antitumor immunity. Immunological recovery of old patients after conventional chemotherapy (CT) has not been fully investigated, while several studies conducted in patients undergoing blood stem cell transplantation have demonstrated that a delayed immune reconstitution associated with older age results in increased susceptibility to opportunistic infections and risk of tumour relapse. Cellular immunotherapy and vaccination are becoming viable options for improving survival and quality of life of cancer patients targeting both the host defences and the tumour. The clinical experience in elderly patients is still in its infancy, but available data indicate that these approaches are feasible and promising. A key problem in the studies on aging, immunity and cancer is that it is difficult to distinguish changes related to age from those related to cancer-dependent immunosuppression, but independent from the age of the subject. Longitudinal studies on aged healthy and cancer persons and the use of new immunological techniques may be required to clarify these issues.
Publisher: Informa UK Limited
Date: 16-05-2017
DOI: 10.1080/17474086.2017.1326815
Abstract: Primary effusion lymphoma (PEL) is a rare B-cell lymphoid neoplasm mainly associated with HIV infection, presenting as pleural, peritoneal, and pericardial effusions. A defining property of PEL is its consistent association with Kaposi sarcoma associated herpesvirus (KSHV) infection, and, in most cases, Epstein Barr virus (EBV) co-infection. On these grounds, a review of the literature related to viral cooperation and lymphomagenesis can help to understand the complex interplay between KSHV and EBV in PEL pathogenesis. Areas covered: In this review, the authors highlight clinical, pathologic, genetic and proteomic features of PEL, in the context of viral cooperation in PEL lymphomagenesis. Expert commentary: Tumour cells are characterized by the overexpression of genes that are involved in inflammation and invasion. Coherently, PEL secretomes are enriched in proteins probably responsible for the particular tropism (cell adhesion and migration) of PEL cells. The development of PEL in HIV+ patients is multifactorial and involves a complex interplay among co-infection with oncogenic viruses (EBV and KSHV), inflammatory factors, and environmental conditions.
No related grants have been discovered for Paolo De Paoli.