Immunotherapy in HIV-associated Kaposi Sarcoma: Challenges and Prospects

Abstract

Kaposi Sarcoma (KS) stems from malignant endothelial cells targeting the cutaneous and lymphatic systems. The aetiological agent, human herpesvirus type 8, has been implicated in the induction of KS. Of the four variants of KS that exist, HIV/AIDS associated KS remains one of the leading cancers in people living with HIV in sub-Saharan Africa (SSA). It is estimated that approximately 80% of KS cases were attributed to HIV in 2020. With the introduction of anti-retroviral therapy (ART) the burden of KS was temporarily alleviated. To date, its prevalence on the continent remains significant in comparison to the rest of the world. Traditional therapeutics such as chemotherapy continue to be the most common form of managing HIV-associated KS; however, the incidence of this global cancer continues to rise, predominantly in SSA. Furthermore, a significant number of HIV/AIDS-associated KS patients had been observed with normal CD4+ count and low viral load levels. This necessitates the development of other therapeutic strategies to collectively manage the continental crisis. Various strategies, such as immunomodulatory agents, monoclonal antibodies and therapeutic cytokines, are being investigated to be used as potential therapeutic strategies. One strategy highlights targeting the signalling pathways and growth factors involved in angiogenesis, which is an important characteristic of KS. The PD-1/PD-L1 immune checkpoint blockades are particularly interesting since cell cycle inhibitors have shown promising results as a potential immunotherapeutic agent. Predictive biomarkers and alternative vaccines will be discussed here while potential barriers which reduce the impact of immunotherapy are discussed throughout the review.