Abstract A042: Characterization of the hormone receptor-positive breast tumor immune microenvironment using single cell transcriptomics and multiplex immunofluorescence

Abstract

Abstract Hormone receptor-positive (HR+) breast tumors are the most frequently diagnosed type of breast cancer (~70%) and are characterized by the expression of the estrogen receptor and/or the progesterone receptor. HR+ breast tumors derive limited benefit from immune checkpoint therapy (ICT), which can be at least partially attributed in part, to low levels of T cell infiltration and low expression of T cell immune checkpoint molecules. In other solid tumors, targeting components of the tumor microenvironment outside of T cells have shown the ability to enhance ICT responses, however, such targets have been relatively unexplored in HR+ breast cancer. We hypothesize that there are unidentified targetable non-lymphocyte immune populations within the HR+ breast tumor microenvironment, which can be targeted to increase response to ICT. We performed paired bulk RNA sequencing and cyclic immunofluorescence (CyCIF) from untreated human HR+ tumors (n=30) as well as single-cell RNA sequencing (scRNA-seq) on a subset (N=17) of the tumors, to characterize the spatial composition of the immune infiltrate and identify gene expression profiles that correlate with T cell infiltration. We have identified tumor-associated macrophages (TAMs) as being the immune cell population most abundant in HR+ tumors by both scRNA-seq & CyCIF. We identified SPP1+ CD36+ expressing macrophages to be significantly enriched in T cell-low compared to T cell-high HR+ tumors. These SPP1+ CD36+ macrophages have been previously linked to lipid metabolism in the tumor microenvironment and we confirmed such with gene set enrichment analysis. Inversely, T cell high HR+ tumors displayed a significant enrichment of MUCL1+APOD+ macrophages expressing high levels of MHC class II molecules and enriched for gene sets relating to antigen presentation and interferon responses. Collectively, these findings put forth two populations of macrophages within HR+ tumors as novel immunotherapeutic targets for further investigation to enhance T cell responses and ICT. Citation Format: Daniel Michaud, Kenichi Shimada, Kelly Zheng, Cheryl Gu, Yvonne Cui, Jonathan Goldberg, Esther Ogayo, Peter Sorger, Sandro Santagata, Elizabeth Mittendorf, Jennifer Guerriero. Characterization of the hormone receptor-positive breast tumor immune microenvironment using single cell transcriptomics and multiplex immunofluorescence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A042.