Abstract 2555: Immunophenotyping early stage lung adenocarcinomas (LUAD) by histologic subtype

Abstract

Abstract The immune microenvironment is thought to influence Lung Adenocarcinoma (LUAD) subtype formation, disease progression, and thus patient outcome. Despite recent advancements in screening, immunotherapy, and targeted therapy, the biology of aggressive LUAD is still poorly understood, and in-depth characterization associated with LUAD histologic subtypes and progression are needed. In this study, we sought to measure the immune environment associated with different LUAD subtypes using Imaging Mass Cytometry (IMC). IMC has emerged as a powerful new tool that enables the multiplex imaging of more than 50 markers simultaneously, quantify multiple protein expressions at a single cell level, and preserve tissue spatial information. We stained a tissue microarray of early stage LUAD patient samples, representing different LUAD subtypes, with a panel of 21 antibodies. These antibodies are designed to phenotype immune cell subsets, as well as using Ki67 to stain for highly proliferative epithelial cells. This will allow us to better understand how different immune cells are interacting with each other, as well as how they interact with highly proliferating epithelial cells. The resulting ablated samples generate images containing antibody intensity and coordinates, which we then perform cell segmentation to generate single cell data. The marker expression is then quantified, and single cell data analyzed using HistoCAT. Cell neighborhood interactions are analyzed based on spatial relationships, and similarly interacting cells are grouped into phenoclusters. Our results suggest that a Ki67 high phenocluster within solid LUAD subtypes have fewer macrophages (CD68, CD163) and T cell populations (CD8, CD4, FOXP3), however, are enriched for plasma B cells (CD20) and immune suppressive populations (PD1, PDL1). In contrast, a Ki67 high cluster within lepidic subtypes are enriched for of macrophage (CD68) and T cell populations (CD8, CD4, FOXP3). Using IMC, we have begun to identify immune subset shifts in LUAD. This early analysis of LUAD using IMC begins to shed light on the immune regulation that may indicate progression and/or guide intervention approaches. Citation Format: Zhanhao Xi, Roxana Pfefferkorn, Eric Burks, Jennifer Beane, Sarah Mazzilli. Immunophenotyping early stage lung adenocarcinomas (LUAD) by histologic subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2555.