Evaluation of immune microenvironement in patients with non-small-cell lung cancer and HIV infection
April 01, 2021
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.
