TH1/17 hybrid CD4+ cells in bronchial alveolar lavage fluid from leukemia patients with checkpoint inhibitor-induced pneumonitis.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 204-204
Author(s):  
Sang Kim ◽  
Vickie Shannon ◽  
Ajay Sheshadri ◽  
Hagop M. Kantarjian ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Cell Biology ◽  
Myeloid Leukemia ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Statistical Significance ◽  
Standard Of Care ◽  
Lavage Fluid ◽  
Cd4 Cells ◽  
Bronchial Alveolar Lavage Fluid ◽  
Bronchial Alveolar Lavage

204 Background: Immune checkpoint inhibitor (ICI)-based therapies are showing encouraging results for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). 20% of AML or MDS patients receiving an ICI develop lung inflammation (herein, pneumonitis), one of fatal immune related adverse events (irAEs). The mechanisms of pneumonitis, the most important step for risk stratification and early detection, remain elusive. Methods: We analyzed bronchial alveolar lavage (BAL) fluid from 8 AML or MDS patients, who received an ICI, developed respiratory symptoms, and underwent a standard-of-care bronchoscopy. As a control, we analyzed BAL fluid from 5 AML or MDS patients who had never received an ICI or had received last ICI more than 16 weeks prior to the bronchoscopy. We also analyzed matched blood within 72 hours after the bronchoscopy. We stained CD4+ cells with lineage specific markers, including CXCR3, CXCR5, CD25, CD127, CCR4, and CCR6. Proportion of the CD4+ cell subsets within total CD4+ lymphocytes in BAL and blood were compared between the pneumonitis and controls. Results: Th1 (CXCR3hi) CD4+ cells were expanded in controls in BAL (pneumonitis versus control, 4.2 ± 2.5 % versus 17.2 ± 6.3 % within total CD4+ lymphocytes, P= 0.04) and blood (pneumonitis versus control, 0.5 ± 0.3 % versus 4.0 ± 1.3 % within total CD4+ lymphocytes, P= 0.01). In contrast, Th1/17 (CXCR3hi CCR6hi) hybrid CD4+ cells, known to be pathogenic in autoimmune diseases, were expanded in BAL from the pneumonitis group (pneumonitis versus control, 40.3 ± 8.4 % versus 13.7 ± 4.5 % within total CD4+ lymphocytes, P= 0.03). Th1/17 hybrid CD4+ cells were also PD-1hi Ki67hi, suggesting their hyperactive status. Though not reached statistical significance, regulatory T cells were decreased in BAL from pneumonitis group (pneumonitis versus control, 20.8 ± 4.9 % versus 26.2 ± 9.2 % within total CD4+ lymphocytes). Conclusions: These results suggest that Th1/17 hybrid CD4+ cells may play a central role in pneumonitis. Understanding of the Th1/17 hybrid CD4+ cell biology will provide therapeutic targets and reliable biomarkers for pneumonitis.

Th1/17 Hybrid CD4 + Cells Are Expanded in Bronchial Alveolar Lavage Fluid from Leukemia Patients with Checkpoint Inhibitor-Induced Pneumonitis

2017 ◽  
Vol 17 (10) ◽  
pp. S10 ◽  
Author(s):  
Sang Kim ◽  
Vickie Shannon ◽  
Ajay Sheshadri ◽  
Hagop Kantarjian ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Checkpoint Inhibitor ◽  
Lavage Fluid ◽  
Cd4 Cells ◽  
Bronchial Alveolar Lavage Fluid ◽  
Bronchial Alveolar Lavage

scholarly journals Diagnosis, monitoring, and management of adverse events from immune checkpoint inhibitor therapy

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
O.F. Khan ◽  
J. Monzon
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Early Recognition ◽  
Case Reports ◽  
Standard Of Care ◽  
Health Care Team ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitor therapy (ICIT) is now standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, it is imperative to understand the timing, epidemiology, monitoring, diagnosis, and management of immune related adverse events (irAEs) associated with ICIT. This article reviews specific irAEs by organ system, consolidating recommendations from multiple guidelines and incorporating data from case reports to highlight additional evolving therapeutic options for patients. Managing these adverse events requires early recognition, early intervention, and education of both patients and the multidisciplinary health care team. Given the durable responses observed with ICIT, and the irreversible nature associated with some of these irAEs, further research into management of the sequelae of ICIT is required.

scholarly journals SELECTIVE EFFECTS OF PULMONARY SURFACTANT ON VARIOUS SUBPOPULATIONS OF ALVEOLAR MACROPHAGES IN THE MODEL OF EXPERIMENTAL TUBERCULOSIS

2012 ◽  
Vol 67 (11) ◽  
pp. 22-28 ◽  
Author(s):  
V. V. Erokhin ◽  
L. N. Lepekha ◽  
M. V. Erokhina ◽  
I. V. Bocharova ◽  
A. V. Kurynina ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Phagocytic Activity ◽  
Pulmonary Surfactant ◽  
Lavage Fluid ◽  
Ultrastructural Changes ◽  
Experimental Tuberculosis ◽  
Bronchial Alveolar Lavage Fluid ◽  
Tem Method ◽  
High Level ◽  
Bronchial Alveolar Lavage

Pulmonary surfactant is necessary component for maintenance of high level of phagocytic activity of alveolar macrophages. Tuberculosis inflammation reduces the production of surfactant by type II cells and phagocytic activity of alveolar macrophages. The effects of exogenous pulmonary surfactant on the ultrastructural changes of various subpopulations of alveolar macrophages were studied by TEM-method. For investigations the bronchial alveolar lavage fluid from guinea pigs infected of M. tuberculosis and treated by isoniazid or isoniazid + exogenous pulmonary surfactant were used. It was shown that isoniazid + exogenous pulmonary surfactant normalizes the heterogeneous population of alveolar macrophages providing stimulating effects on their maturation and phagocytic activity more effectively than isoniazid therapy. 

scholarly journals Rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis: a single-center retrospective cohort study

2021 ◽  
Vol 9 (4) ◽  
pp. e002292
Author(s):  
Meghan D Lee ◽  
Harish Seethapathy ◽  
Ian A Strohbehn ◽  
Sophia H Zhao ◽  
Genevieve M Boland ◽  
...  
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Immune Checkpoint ◽  
Retrospective Cohort ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Standard Of Care ◽  
Renal Recovery ◽  
Care Group ◽  
Significant Difference

BackgroundCurrent guidelines for treatment of immune checkpoint inhibitor (ICI)-induced nephritis are not evidence based and may lead to excess corticosteroid exposure. We aimed to compare a rapid corticosteroid taper to standard of care.MethodsRetrospective cohort study in patients with ICI-induced nephritis comparing a rapid taper beginning with 60 mg/day prednisone and tapered to 10 mg within 3 weeks to a historical control group that began 60 mg/day tapered to 10 mg within 6 weeks (standard of care). Renal recovery was defined as creatinine returning to within 1.5-fold baseline. The log-rank test compared the differences in time to renal recovery between the groups. We report rates of renal recovery at 30, 60 and 90 days, and timing and outcomes of ICI rechallenge.ResultsThirteen patients received rapid corticosteroid taper and 14 patients received standard of care. Baseline characteristics were similar between groups. The median time to ≤10 mg/day prednisone was 20 days (IQR 15–25) in the rapid-taper group compared with 38 days (IQR 30–58) in the standard-of-care group. There was no significant difference in the time to renal recovery between the groups, though numerically higher numbers of patients recovered by 30 days, 11 (85%) in the rapid-taper arm versus 6 (46%) in the standard of care arm. Exposure to other nephritis-causing medications (proton pump inhibitor or trimethoprim-sulfamethoxazole) during the corticosteroid taper was more common in the standard of care group, 9 (64%) versus rapid-taper group, 2 (15%), and was associated with longer time to renal recovery, 20 days (IQR 14–101) versus 13 days (IQR 7–34) in those that discontinued nephritis-causing medications. Fifteen (56%) of patients were rechallenged with ICIs, and only two (13%) developed recurrent nephritis.ConclusionsPatients with ICI-induced nephritis have excellent kidney outcomes when treated with corticosteroids that are tapered over 3 weeks.

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