Olingy, Claire, Alimadadi, Ahmad, Araujo, Daniel J, Barry, David, Gutierrez, Norma A, Werbin, Max Hardy, Arriola, Edurne, Patel, Sandip Pravin, Ottensmeier, Christian H 
ORCID: 0000-0003-3619-1657, Dinh, Huy Q et al (show 1 more authors)
(2022)
CD33 Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-PD-1 Immunotherapy Against Non-Small Cell Lung Cancer.
FRONTIERS IN IMMUNOLOGY, 13.
842653-.
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CD33 Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-PD-1 Immunotherapy Against Non-Small Cell Lung Cance.pdf - Published version Download (7MB) | Preview |
Abstract
Non-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<sup>+</sup> nonclassical monocytes, and CD33<sup>hi</sup> classical monocytes. Using matched pre-post treatment samples, we found that the baseline pre-treatment frequencies of CD33<sup>hi</sup> 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<sup>+</sup>FOXP3<sup>+</sup>CD25<sup>+</sup>) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CD33, monocytes, immunotherapy, non-small cell lung cancer, immunosuppression |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Oct 2022 08:18 |
| Last Modified: | 18 Jan 2023 20:36 |
| DOI: | 10.3389/fimmu.2022.842653 |
| Open Access URL: | https://doi.org/10.3389/fimmu.2022.842653 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165568 |
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