Onyinyechi Onyeador
Program: Immunology
Current advisor: Brett Herzog, MD,PhD
Undergraduate university: Washington University
Research summary
Lung cancer is the most common cause of cancer-related mortality worldwide. Immune checkpoint inhibition, though revolutionary, is beneficial for only a subset of patients with metastatic non-small cell lung cancer (NSCLC). Nearly 80% of those diagnosed with advanced stage NSCLC die from their disease within 5 years of diagnosis. The tissue microenvironment of human NSCLC is characterized by a dense stromal network. Our laboratory has demonstrated that CAFs can impair response to anti-tumor immunity in models of NSCLC. A particular subset of CAFs known as PDGFRa identified by our lab appears to impair anti-tumor immunity through reduced infiltration and altered function of T cells. Based on these observations, we hypothesize that PDGFRa CAFs influence anti-tumor immunity by modulating T cell function and/or exclusion, and we seek to understand the mechanism(s) regulating this interaction. For these studies, we will utilize a genetically engineered mouse model (GEMM) of human lung adenocarcinoma, the most common type of NSCLC, which expresses a model antigen, as well as a GEMM of PDGFRa CAF depletion transplanted with a cancer cell line derived from the NSCLC GEMM, which will enable us to assess PDGFRa CAF-mediated immune responses. The identification of the cellular and molecular mechanisms by which PDGFRa CAFs impact T cell-mediated anti-tumor immunity has clinically relevant implications with respect to the development of novel immunotherapy strategies for patients with NSCLC.
Graduate publications
Ramirez CA, Becker-Hapak M, Singhal K, Russler-Germain DA, Frenkel F, Barnell EK, McClain E, Desai S, Schappe T, Onyeador OC, Kudryashova O, Belousov V, Bagaev A, Ocheredko E, Kiwala S, Hundal J, Skidmore ZL, Watkins MP, Mooney TB, Walker J, Krysiak K, Gomez F, Fronick CC, Fulton RS, Schreiber RD, Mehta-Shah N, Cashen AF, Kahl BS, Ataullakhanov R, Bartlett NL, Griffith M, Griffith OL, Fehniger TA. 2024 Neoantigen Landscape Supports Feasibility of Personalized Cancer Vaccine for Follicular Lymphoma. Blood Adv, 8(15):4035-49.