Abstract

HIV infection is associated with an increased risk of lymphomas, presenting a therapeutic challenge due to the complex interplay between immune dysfunction and tumorigenesis. The programmed cell death protein 1 (PD-1) pathway has emerged as a pivotal immune checkpoint involved in the pathogenesis of HIV-related lymphomas, offering a promising target for immunotherapy. In this review, we provide a comprehensive overview of the role of PD-1 and immune checkpoint inhibitors in HIV-related lymphomas, exploring their impact on lymphoma pathogenesis, treatment strategies, and future directions. We discuss the dysregulation of the PD-1 pathway in lymphoma microenvironment, immune evasion mechanisms, and the potential of PD-1 blockade to restore antitumor immunity. Clinical applications of PD-1 inhibitors, including pembrolizumab and nivolumab, in relapsed/refractory HIV-related lymphomas are highlighted, along with challenges such as patient selection, biomarker identification, and treatment resistance. Finally, we discuss future directions for research, emphasizing the need for biomarker-guided approaches, combination therapies, and long-term safety and efficacy data to optimize the integration of PD-1-based immunotherapy into the treatment paradigm of HIV-related lymphomas. This review provides insights into the current landscape of PD-1-based immunotherapy in HIV-related lymphomas and underscores its potential to improve outcomes for individuals living with HIV/AIDS and lymphomas.