Postdoctoral Fellows
National Cancer Institute
Project Title: “Contribution of genetic ancestry to differences in the immune landscape of lung cancer in European Americans and African Americans.”
Immunotherapy was recently adopted as standard of care for the 70-85% of non-small cell lung cancer patients that do not respond to traditional chemotherapy. However, only around 1 in 5 patients are “responsive”, meaning that they experience a durable clinical benefit. There is evidence that the composition of immune cells within the tumor microenvironment influences clinical response to immunotherapy. Most of the knowledge of tumor immune landscape in lung cancer has been obtained from patients of European ancestry. To date, very little work has been done comparing the immune landscape in lung tumors from European Americans (EA) with African Americans (AA) to establish the relationship between the immune landscape, race and genetic ancestry. Identifying population-level differences in the tumor immune microenvironment could have significant implications for immunotherapy response and precision medicine.
Transcriptional differences in immune response are regulated by genetic and epigenetic mechanisms, some of which can differ by genetic ancestry. Findings from epidemiological and functional genomic studies have shown that AAs tend to have a hyper pro-inflammatory transcriptional response to immune stimulation compared with EAs. The awardees’ previous research has identified several macrophage-associated proteins associated with lung cancer only among AAs. Their research has also suggested that lung tumors in AAs have greater fractions of follicular helper T cells and macrophages than tumors of EA origin.
The awardees propose to compare lung tumor and adjacent non-tumor tissue of EA and AA patients to delineate immune cell subsets enriched in the tumor, and tumor-infiltrating immune cell composition to identify population-level differences. They will also determine tumor-infiltrating immune cell composition and neoantigen load, and how these immune factors differ by genetic ancestry. By characterizing these population-level immune-dependent differences, they hope to contribute to a more precise determination of biomarkers to inform precision medicine that adequately represents AAs.
