التفاصيل البيبلوغرافية
| العنوان: |
The alveolar immune cell landscape is dysregulated in checkpoint inhibitor pneumonitis. |
| المؤلفون: |
Suresh, Karthik1 ksuresh2@jhmi.edu, Naidoo, Jarushka2,3, Qiong Zhong1, Ye Xiong1, Mammen, Jennifer4, Villegas de Flores, Marcia5, Cappelli, Laura5, Balaji, Aanika2, Palmer, Tsvi1, Forde, Patrick M.2,3, Anagnostou, Valsamo2,3, Ettinger, David S.2, Marrone, Kristen A.2,3, Kelly, Ronan J.2,3, Hann, Christine L.2,3, Levy, Benjamin2,3, Feliciano, Josephine L.2,3, Cheng-Ting Lin6, Feller-Kopman, David1, Lerner, Andrew D.1 |
| المصدر: |
Journal of Clinical Investigation. Oct2019, Vol. 129 Issue 10, p4305-4315. 11p. |
| مصطلحات موضوعية: |
*PNEUMONIA, *CELL populations, *T cells, *SUPPRESSOR cells, *BRONCHOALVEOLAR lavage, *MENTAL foramen, *TUMOR treatment, *ANTIGENS, *COMPARATIVE studies, *CYTOKINES, *IMMUNOTHERAPY, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *PULMONARY alveoli, *RESEARCH, *TUMORS, *EVALUATION research |
| مستخلص: |
Background: Checkpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy (ICI), one which precludes the continuation of ICI. Yet, the mechanistic underpinnings of CIP are unknown.Methods: To better understand the mechanism of lung injury in CIP, we prospectively collected bronchoalveolar lavage (BAL) samples in ICI-treated patients with (n=12) and without CIP (n=6), prior to initiation of first-line therapy for CIP (high dose corticosteroids. We analyzed BAL immune cell populations using a combination of traditional multicolor flow cytometry gating, unsupervised clustering analysis and BAL supernatant cytokine measurements.Results: We found increased BAL lymphocytosis, predominantly CD4+ T cells, in CIP. Specifically, we observed increased numbers of BAL central memory T-cells (Tcm), evidence of Type I polarization, and decreased expression of CTLA-4 and PD-1 in BAL Tregs, suggesting both activation of pro-inflammatory subsets and an attenuated suppressive phenotype. CIP BAL myeloid immune populations displayed enhanced expression of IL-1β and decreased expression of counter-regulatory IL-1RA. We observed increased levels of T cell chemoattractants in the BAL supernatant, consistent with our pro-inflammatory, lymphocytic cellular landscape.Conclusion: We observe several immune cell subpopulations that are dysregulated in CIP, which may represent possible targets that could lead to therapeutics for this morbid immune related adverse event. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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