505 High-dimensional analyses of intratumoral myeloid cells highlights presence of distinct myeloid cell phenotypes in immune checkpoint-sensitive and resistant tumors

Abstract

Background Immune checkpoint therapy (ICT) has revolution-ized cancer treatment, however, has produced around 20% durable clinical response rates. 1 Multiple studies demonstrate myeloid cell abundance and function in the tumor microenvir-onment (TME) correlates with poor outcome in ICT resistant cancers. 2, 3 Despite the wealth of knowledge regarding the biology of these cells, our ability to distinguish immune-sup-pressive versus immune-stimulatory myeloid cells remains a major challenge and, thus, targeting myeloid cells has had lim-ited clinical success. Our objective is to better understand the phenotype of these immunosuppressive myeloid cells to identify potential combination strategies to improve response to ICT. Methods Comparative analyses of intratumoral myeloid cell subsets was performed in orthotopic murine models of ICT sensitive (B16F10 melanoma) and resistant (MT4 pancreatic) tumors at baseline and post ICT treatment (anti-PD-1 and/or anti-CTLA-4 antibodies) using single cell RNA sequencing (scRNAseq). To determine myeloid cell evolution with tumor progression, longitudinal scRNAseq was performed on MT4 tumors.