Effects of HIV on the Tumor Microenvironment

Abstract

Oncomodulatory viruses can affect the tumor microenvironment (TME) by triggering inflammation, suppressing apoptosis, initiating angiogenesis, altering tumor metabolism, and stimulating tumor cell signaling pathways, leading to tumor growth, proliferation, and invasion. The higher incidence of malignancies among people with HIV (PWH), despite the widespread use of antiretroviral therapy (ART), suggests a more complex relation than HIV-associated immune deregulation. Viral cooperation can have synergistic effect on tumorigenesis. The most relevant oncogenes involved in viral cooperation include the HIV-1-related Tat and Vpu genes, EBV LMP-1 and EBNA-2 genes, and Kaposi’s sarcoma herpesvirus (KSHV) KIE2, Rta, and LANA genes. The TME in HIV-related malignancies is highly angiogenic and characterized by high microvessel density compared to sporadic cases. Tat protein, found in patients with HIV infection regardless of their immune status, has been widely implicated in the increased angiogenesis and has been a target of interest for therapeutic strategies. Similarly, HIV-1 matrix protein p17 can be detected in the plasma and tissues of PWH, including those treated with ART. Studies have found that p17 can cause dysregulation of the biological activity of different immune cells, is involved in aberrant angiogenesis, and exhibits an IL8 chemokine activity, activating multiple intracellular signaling pathways, promoting angiogenic responses in endothelial cells, and forming capillary like structures. In addition, several studies have demonstrated difference in the cellular immune components within the TME in patients with or without HIV infection, as well as cases in pre- and post-ART era. In this chapter, we review the existing literature about the role tumor microenvironment plays in the pathogenesis of HIV-related malignancies. Understanding the functions of each component of the TME and determining how these cellular and noncellular components contribute to tumorigenesis will impact the advancement of interventions and treatment in clinical oncology among PWH.