Abstract 5883: Computational analysis of immune synapses in melanoma tumor microenvironment

Abstract

Abstract High-resolution multiplexed tissue imaging such as imaging mass cytometry (IMC) has enabled quantitative cell characterization with preserved tissue architecture. However, the subcellular resolution information has not been fully leveraged yet, as most analyses have focused on cellular or compartment level features. Here, we have developed a robust computational approach integrating cellular spatial and molecular features in multiplexed images to quantify immune synapses. Our approach enables computational detection of subcellular enrichment of T cell co-receptors at immune synapses, which are key regulators of T cell functions in the tumor microenvironment (TME). We quantified immune synapse strength between T cells and various antigen-presenting cells in tumor regions in one melanoma whole tissue immunofluorescence dataset and two independent melanoma IMC datasets covering 99 patients. We observed that sub-localizations of immune synapse-related molecules are highly correlated, e.g. CD3 with CD8. These co-localizations are cell type-specific, with differential behaviors in CD4+ or CD8+ T subtypes. Intra-tumoral T-cell-myeloid synapses are associated with improved T cell proliferation (p = 2.8E-4). In addition, we also observed that cytotoxic T cell - melanoma synapses in immune rich regions are stronger in immune checkpoint inhibition therapy responders than in non-responding patients (p = 0.013). Our approach enables computational resolution of spatial inter-cellular interactions within the TME, is applicable across imaging modalities, and facilities assessment of biological and clinical significance. Citation Format: Zichao Liu, Victor G. Wang, Jan Martinek, Ali Foroughi pour, Jie Zhou, Karolina Palucka, Jeffrey H. Chuang. Computational analysis of immune synapses in melanoma tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5883.