Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade

Rationale: Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. Objectives: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. Methods: The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T-cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with NSCLC and patients with melanoma. Measurements and Main Results: Across both cohorts, patients in whom pneumonitis developed had higher pretreatment levels of immunoglobulin G autoantibodies targeting surfactant protein (SP)-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4(+) IFN-

• Wyss, N.
• Berner, F.
• Walter, V.
• Jochum, A. K.
• Purde, M. T.
• Abdou, M. T.
• Sinnberg, T.
• Hofmeister, K.
• Pop, O. T.
• Hasan Ali, O.
• Bauer, J.
• Cheng, H. W.
• Lütge, M.
• Klümper, N.
• Diem, S.
• Kosaloglu-Yalcin, Z.
• Zhang, Y.
• Sellmer, L.
• Macek, B.
• Karbach, J.
• König, D.
• Läubli, H.
• Zender, L.
• Meyer, B. S.
• Driessen, C.
• Schürch, C. M.
• Jochum, W.
• Amaral, T.
• Heinzerling, L.
• Cozzio, A.
• Hegazy, A. N.
• Schneider, T.
• Brutsche, M. H.
• Sette, A.
• Lenz, T. L.
• Walz, J.
• Rammensee, H. G.
• Früh, M.
• Jäger, E.
• Becher, B.
• Tufman, A.
• Nuñez, N.
• Joerger, M.
• Flatz, L.