Overcoming Anti-PD-1 Resistance in Lung Cancer
Abstract
The goal of this proposal was to first define the cellular and molecular effector mechanisms that underlie our original observation, i.e. lung Th17 immunity drives anti-PD-1 resistance in lung cancer (Aim1); and then determine whether the lung microbiota signature ultimately determines the severity of Th17 cell activity (Aim 2). To this end, we have constructed a genetic model that will allow us to test the central hypothesis, i.e. lung Th17 cells are the primary drivers of resistance to anti-PD-1 (Aim 1a). This model is now being assessed for functionality prior to directly testing the above notion. In addition, we found that the post-anti-PD-1 treatment Th17 cell prevalence in the cancerous lung is predictive of treatment outcome (Aim 1b). Finally, we have found that lung MDSC activity does not explain the anti-PD-1-Th17 cell driven treatment resistance (Aim 1ci) and are now exploring the other alternative mechanisms (Aim 1cii-iv). In the coming year we plan to conclude remaining Aim 1work and initiate Aim 2 studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1114478
Entities
People
- Nejat K Egilmez
Organizations
- University of Louisville