Grant: Master's Award: Canada Graduate Scholarships

Novel biomarkers are needed to better predict anti-PD-1 response in non-small cell lung carcinoma (NSCLC) patients. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as key players in checkpoint blockade resistance. Subtypes include monocytic M-MDSCs and granulocytic G-MDSCs, which are phenotypically similar to monocytes and neutrophils respectively. While pre-clinical evidence has shown that high levels of circulating G-MDSCs predict poor anti-PD-1 response in NSCLC, limited research exists investigating their TME infiltration due to difficulty in isolating subtypes. This study aims to characterize MDSCs within the TME of NSCLC patients using multiplex immunuofluorescence (mIF). We hypothesized that high densities of infiltrating G-MDSCs will be associated with poor anti-PD-1 response. Our goals are to (1) optimize our mIF panel to ensure that staining is highly sensitive and specific (2) quantify cellular densities of MDSC subsets and neutrophils (3) correlate cellular densities with anti-PD-1 response to identify subsets with biomarker potential. mIF staining will be conducted on a cohort of 96 pre-treatment NSCLC specimens with existing response data. Our mIF panel will interrogate the following markers to help distinguish G-MDSC, M-MDSC, neutrophil, and tumour lineages: CD14, CD15, CD11b, Lox1, Arg-1, IDO1, and AE1AE3 (tumour). In collaboration with Johns Hopkins University, mIF analysis will be conducted using their Astropath pipeline. Resulting density data for each cellular population will then be assessed in responders and non-responders. If our hypothesis holds true, then infiltrating G-MDSCs may serve as an alternative predictive anti-PD-1 biomarker in NSCLC.