39 A multi-modal analysis approach leveraging multiplexed spatial phenotyping and multi-omics analysis to better understand the prognostic value of tertiary lymphoid structures in NSCLC

Background Tertiary Lymphoid Structures (TLS) are highly organized ectopic lymphoid structures found in inflamed or tumor tissues, acting as sites of recruitment and immune activation. A high TLS density within the is commonly associated with an increased prognostic effect TILs improved disease free survival overall for patients. 1 However, existence conflicting studies suggest that multiple features should be taken into account when assessing their value, such location, cellular composition, maturation stage spatial organisation, those may affect functionalities. 2 Methods With aim gaining insights biology evaluating role Non-Small Cell Lung Carcinoma according to features, we developed a multiplex immunofluorescent (mIF) panel includes T cells (CD3, CD8), B (CD20), Follicular Dendritic (CD21, CD23) mature dendritic (DC-LAMP) markers. We deployed this across cohort primary tumors from NSCLC patients (n=408) established mIF image analysis workstream assess status location each cell tissue. H&E staining same tissue section was performed evaluate data relation context. Additional multi-omics assessments were conducted including; whole exome sequencing, NanoString transcriptomics, immunohistochemistry (e.g. PD-L1, FOXP3, NKp46, LKB1, CTLA4). have leveraged clinical metadata, including demographics age, sex, smoking status) risk factors stage, grade, Standard Care treatment) follow up OS, PFS) prevalence analysis, novel biomarker identification, association. Results Assessment phenotype TLS, cell-cell interactions, distance between type, non-TLS closest will described, demonstrating different types aggregates functional status. An integrative combining presented value organization, correlation additional biomarkers characteristics. Conclusions This exploratory study using cutting-edge technologies enables us better understand how orchestrate organised anti-tumour response, defining signatures, gene patient outcomes clinic. References Marie-Caroline Dieu-Nosjean, Jérémy Goc, Nicolas Giraldo, Catherine Sautès-Fridman, Wolf Herman Fridman. cancer beyond. Trends Immunol 2014; 35 (11):571–580. Florent Petitprez, Julien Calderaro, era immunotherapy. Nat Rev Cancer 2019; 19 (6):307–325. Ethics Approval The approved by AstraZeneca.