Lung cancer is one most common non-AIDS defining cancer (NADC) and the leading cause of cancer death in HIV infected population since the introduction of combination antiretroviral therapy (cART) in 1996. The average age at lung cancer diagnosis is younger and their prognosis is worse in HIV infected patients than in the general population. Despite recent breakthroughs in immunotherapy, it is unknown whether cancer patients with HIV are good candidates for immunotherapy, since they are often excluded from cancer immunotherapy studies. To identify biomarkers useful for HIV-associated lung cancer early detection, progression, and response to treatment, particularly immunotherapy, to understand HIV-associated lung cancer molecular pathogenesis, and to determine similarities and differences between lung cancer in HIV-infected and uninfected individuals, we will examine and compare the immune profiles, gene expression, genomic mutations, and microbiome in specimens from lung cancer patients with and without HIV infection. These studies will not only provide important insight into HIV-associated lung cancer pathogenesis and help to improve its diagnosis, prognosis, and treatment, but also shed light on the pathogenesis, diagnosis, prognosis, and treatment of HIV-associated other malignancies.