University of Pittsburgh Cancer Institute (UPCI)

AIDS-related and Other Immunodeficiency Malignancies (ARM)

AIDS-related cancers are now the most common malignancies in sub-Saharan Africa. UPCI is one of the leading centers for AIDS-related malignancy research. The University of Pittsburgh and UPCI have developed a strategic goal to enhance research activities in international settings, and the expertise of the CVP ARM will be an important contributor to this goal.

Human immunodeficiency virus (HIV) itself is classified as an infectious carcinogen by WHO International Agency for Research on Cancer (IARC), primarily due to its capacity to increase risk for opportunistic cancers. The CVP ARM has a strong component investigating the mechanisms for HIV-related immunodeficiency and pathogenesis. Immunosuppressed transplant patients also face many of the same cancer issues as AIDS patients. Members of the ARM investigate the role of immunosuppression in virus-induced tumors and have initiated productive collaborations with the University of Pittsburgh transplantation community on topics such as post-transplant lymphoproliferative disorder (PTLD) pathogenesis and immunity, and KSHV diagnostics for transplantation screening. Additionally, mucosal infection with oncogenic human papillomavirus (HPV) and its link to both dysplasia and malignancy is being investigated in a population of iatrogenically immunosuppressed patients with inflammatory bowel disease.

Selected Publications

• Peptide-based inhibitors to prevent hepatitis C virus infection of cells were identified (Si et. al., Hepatol 2012).
• Mutations in the polymerase but not in connection or RNase H domains of reverse transcriptase gene of the human AIDS virus (HIV-a) increased in frequency between pre-therapy and antiviral therapy failure (Brehm et. al., J Acquir Immune Defic Syndr. 56:344-348, 2011).
• Distinct c-terminal tail topologies for virion- and cell-associated HIV-1 gp41 envelope (Env) protein were found (Steckbeck et. al., PLoS One. 5(12):e15261, 2010).
• An underlying, broad antigenic spectrum of anti-HIV-1, memory CD8⁺ T cell reactivity was found in persons on anti-retroviral therapy of HIV-1 that is revealed by dendritic cells (DC). This supports the use of DC-based immunotherapy for HIV-1 infection (Huang et. al., PLoS One. 5(9):e12936, 2010).

Members

Section Leader: Ross Cranston