Onyinyechi Onyeador
Program: Immunology
Current advisor: Brett Herzog, MD,PhD
Undergraduate university: Washington University
Research summary
Immune checkpoint inhibitors (ICIs) have improved outcomes in many cancers. However, ICIs do not help all patients with non-small cell lung cancer (NSCLC). Even in patients who initially respond, most will eventually progress, demonstrating a significant need to understand and target the mechanisms limiting anti-tumor immunity.
One hypothesis is that this lack of response is due to the presence of an immunosuppressive tumor microenvironment (TME) that either excludes T cell infiltration or limits T cell function. NSCLC has a desmoplastic TME characterized by high cancer-associated fibroblast (CAF) density and extracellular matrix deposition. To better understand this, we generated data in preclinical models and human NSCLC samples showing that tumor-associated fibrosis impairs anti-tumor immunity via reduced T cell infiltration and renders anti-PD1 checkpoint immunotherapy ineffective. Based on these data, we propose the following hypothesis: CAFs impair anti-tumor immunity by impairing T cell localization and function. Therefore, we seek to address the question of how CAFs influence T cell localization and function in the TME. Addressing this question will fill a critical gap in knowledge regarding how immune surveillance is modified by subsets of CAFs and possibly reveal novel targets to enhance ICI-efficacy in 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.