Olingy, ClaireAlimadadi, AhmadAraujo, Daniel J.Barry, DavidGutiérrez, NormaWerbin, Max HardyArriola Aperribay, EdurnePatel, Sandip PravinOttensmeier, Christian H.Dinh, Huy Q.Hedrick, Catherine C.2022-11-032022-11-032022Olingy C, Alimadadi A, Araujo DJ, Barry D, Gutierrez NA, Werbin MH, et al. CD33 expression on peripheral blood monocytes predicts efficacy of anti-PD-1 immunotherapy against non-small cell lung cancer. Front Immunol. 2022 Apr 14; 13: 842653. DOI: 10.3389/fimmu.2022.8426531664-3224http://hdl.handle.net/10230/54671Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related deaths globally. Immune checkpoint blockade (ICB) has transformed cancer medicine, with anti-programmed cell death protein 1 (anti-PD-1) therapy now well-utilized for treating NSCLC. Still, not all patients with NSCLC respond positively to anti-PD-1 therapy, and some patients acquire resistance to treatment. There remains an urgent need to find markers predictive of anti-PD-1 responsiveness. To this end, we performed mass cytometry on peripheral blood mononuclear cells from 26 patients with NSCLC during anti-PD-1 treatment. Patients who responded to anti-PD-1 ICB displayed significantly higher levels of antigen-presenting myeloid cells, including CD9+ nonclassical monocytes, and CD33hi classical monocytes. Using matched pre-post treatment samples, we found that the baseline pre-treatment frequencies of CD33hi monocytes predicted patient responsiveness to anti-PD-1 therapy. Moreover, some of these classical and nonclassical monocyte subsets were associated with reduced immunosuppression by T regulatory (CD4+FOXP3+CD25+) cells in the same patients. Our use of machine learning corroborated the association of specific monocyte markers with responsiveness to ICB. Our work provides a high-dimensional profile of monocytes in NSCLC and links CD33 expression on monocytes with anti-PD-1 effectiveness in patients with NSCLC.application/pdfengCopyright © 2022 Olingy, Alimadadi, Araujo, Barry, Gutierrez, Werbin, Arriola, Patel, Ottensmeier, Dinh and Hedrick. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fimmu.2022.842653CD33ImmunosuppressionImmunotherapyMonocytesNon-small cell lung cancerinfo:eu-repo/semantics/openAccess