TY - JOUR T1 - Lung Cancer-Associated Fibroblasts in MHCII immunity: Understanding its Molecular Basis to Design Novel Immunotherapies JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.LSC-2022.44 VL - 8 IS - suppl 8 SP - 44 AU - Ilias Angelidis AU - Dimitrios Konstandopoulos AU - Dimitra Kerdidani AU - Emmanouil Aerakis AU - Katerina Douka AU - Dorothea Maneta AU - Ioannis Vamvakaris AU - Konstantinos Potaris AU - Konstantinos Vachlas AU - Evangelos Sepsas AU - Maria Tsoumakidou Y1 - 2022/03/10 UR - http://openres.ersjournals.com/content/8/suppl_8/44.abstract N2 - In situ antigen presentation is essential to retain T cells within tumors however the antigen presenting cells and pathways involved are incompletely understood. Recent data indicate that a subset of cancer-associated fibroblasts (CAFs) are induced to present MHCII antigens and prime intratumoral CD4+ T cells in human lung carcinomas (Fig.1). Fibroblast-specific targeted ablation of MHCII impacts tumor-infiltrating CD4+ T cell numbers and metabolic profile, accompanied by an increase in tumor burden. Our study aims to uncover the molecular signature of lung antigen presenting CAFs (apCAFs), providing the basis for their future targeting. Using scRNA sequencing we have so far identified the transcriptional profile of apCAFs in human tumors and have overlayed these signature in paired spatial transcriptomic data. The expression patterns of spatially resolved transcriptoms highlight up-regulated genes in spots that contain adjacent apCAFs and activated CD4+ T cells. To dissect the biological role of candidate genes in apCAF-T cell comunications we intend to knock down promising molecular targets in human derived apCAF and assess T cell activation capacities in cocultures. Our preliminary data challenge the immunological dogma that physiological significance in tumor immunity comes only through professional antigen-presenting cells and refute the general concept that CAFs are immunosuppressive. FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 44.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -