Immune Landscape of Anal Cancer and Survival Outcomes in People with HIV (Immuno/Microenvironment)

Vanderbilt University Medical Center, Nashville TN

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY/ABSTRACT HIV is associated with a 30-fold increased lifetime risk of anal cancer. Altered immunity, not simply immunodeficiency, is one proposed mechanism driving this excess risk, and the significantly worse outcomes observed following a cancer diagnosis compared to individuals without HIV. The immune milieu is likely a major factor contributing to these cancer disparities among people living with HIV (PWH). However, few studies have examined the anal tumor immune landscape by HIV status and the associated with cancer outcomes. Chemoradiation therapy is the standard treatment for anal cancer; however, ~30% of anal cancer cases recur and this is similar for people with and without HIV. Further, treating anal cancer recurrence comes with detrimental side effects and morbidity. The persistence of chemoradiation therapy as the standard of care is due the rarity of anal cancer and the difficulty of completing large, randomized clinical trials. Identification of biomarkers that can predict at-risk individuals with unfavorable treatment outcomes is urgently needed. It is likely that additional molecular events besides HPV are required for anal cancer development and these molecular events are likely associated with disease recurrence. Overall, not much is known about the transcriptomic and immunologic signatures of anal cancer treatment differences. Thus, evaluating the full transcriptomic and immunologic profile of anal cancer tissue would be a logical first step to help elucidate when, where, and to what extent biological aberrations facilitate treatment outcomes for anal cancer. To address the gap in the field, we have established a clinical cohort at Vanderbilt University Medical Center that links to all electronic health record data and tissue biorepository to maximize sample utility with enriched clinical data for this rare cancer. We will conduct the following specific aims using pre-treatment tissues from anal cancer patients with and without HIV: (1) examining differences in the transcriptomic profiling of anal cancer tissue by HIV status identify clinical biomarkers for cancer outcomes using RNA-seq; (2) evaluate differences in tumor immune profiles by HIV status and cancer outcomes using spatial transcriptomics; (3) assess transcriptomic and immunologic biomarkers in longitudinal samples from patients who had recurrent anal cancer. Building upon our preliminary studies in PWH, the proposed innovative study is the first to investigate the immune and transcriptomic landscape of anal cancer recurrence. Results from this study have high translational implications as it will a) will identify at-risk individuals who may require alternate treatment or close monitoring and care management and b) understand the biology of anal cancer and pathogenesis. The biomarkers identified could help to improve cancer treatment targets to inform development of future, more efficacious treatment strategies tailored to anal cancer.