Abstract 73: Targeting B Cells and Tertiary Lymphoid Structures in Lung Cancer Progression

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Abstract Purpose: Immunotherapy has revolutionized treatment options for multiple solid tumors, including non-small cell lung cancer (NSCLC). However, these approaches are only effective in 20-30% of NSCLC patients, thus a more comprehensive picture of the immune response in NSCLC is necessary to develop new therapeutic approaches. Current immunotherapies do not consider or target B cells or tertiary lymphoid structures (TLS) despite their predominance in the tumor microenvironment (TME) and key role in the adaptive immune response. We hypothesize that B cells help generate potent, long-term, immune responses against lung tumor cells by educating T cells within TLS and producing tumor-specific antibodies. Methods: Toward our hypothesis, we have evaluated B cells and TLS in healthy donor lungs (smoker and nonsmoker), COPD patients, and NSCLC patients via single cell RNA sequencing, spectral cytometry (Cytek Aurora) and multispectral imaging (Vectra Polaris and Nanostring GeoMx DSP). These cellular and spatial analyses have revealed key differences in B cell infiltration and TLS formation as lung cancer develops. Results: We have observed an increase in mature TLS (with active germinal centers) as patients develop cancer and have identified key genes that govern TLS heterogeneity in the TME. Further, in evaluating the ex vivo function of B cells from patient tumors via antigen presentation and antibody production assays, we have observed differential function of B cells that correlates with B cell activation (increased HLADR, CD40, CD69). Conclusions: Our studies will provide (a) biomarkers to predict lung cancer progression, (b) targets for early immunotherapeutic intervention in COPD patients that might trigger better anti-tumor immunity as patients develop lung cancer, and (c) immunotherapeutic targets in patients with already established NSCLC. Citation Format: Tullia Bruno, Dongyan Liu, Sheryl Kunning, Riyue Bao, Laura Stabile, Ashwin Somasundaram. Targeting B Cells and Tertiary Lymphoid Structures in Lung Cancer Progression [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 73.