Pilot Award Recipient: Chul Kim, MD, MPH

People living with HIV (PLWH) are at risk for developing diverse malignancies. Among the cancers that can arise in PLWH, lung cancer is a leading cause of morbidity and mortality. When compared with the general lung cancer population, PLWH who are diagnosed with lung cancer are younger and have poorer outcomes even when they receive stage-appropriate treatment for their lung cancer. While chronic inflammation and decreased immune surveillance associated with HIV infection have been suggested as potential mechanisms of lung cancer initiation and metastatic progression in PLWH, whether and to which extent HIV-associated systemic immune dysregulation affects the local immune response in the tumor microenvironment has not been fully evaluated. With the success of cancer immunotherapy such as immune checkpoint inhibitor therapy in the treatment of various cancer types including lung cancer, it has become increasingly important to understand the interactions between the immune system and cancer cells by comprehensively profiling the local immune response in the tumor microenvironment. Elucidation of the tumor immune microenvironment in PLWH suffering from nonsmall-cell lung cancer (NSCLC) – the most common type of lung cancer – will deep our understanding of HIV-driven lung cancer tumorigenesis and progression and allow us to devise novel immunotherapeutic approaches designed specifically for PLWH. In this study, we propose to interrogate the expression of inhibitory immune checkpoints and immune cell populations in the tumor microenvironment in HIV-associated and HIV-unassociated NSCLCs, utilizing multiplexed imaging mass cytometry technology (Fluidigm, USA). We will also evaluate the presence of HIV infection in the tumor microenvironment and its impacts on the local immune response using RNAscope in situ hybridization (ACDbio, USA). In the long term, the results of the study have the potential to lay the foundation for development of novel immunotherapeutic strategies in PLWH and NSCLC.