Literature DB >> 33552049

Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications.

Sang T Kim1, Ajay Sheshadri2, Vickie Shannon2, Dimitrios P Kontoyiannis3, Hagop Kantarjian4, Guillermo Garcia-Manero4, Farhad Ravandi4, Jin S Im5, Prajwal Boddu4, Lara Bashoura2, Diwakar D Balachandran2, Scott E Evans2, Saadia Faiz2, Wilfredo Ruiz Vazquez5, Margarita Divenko6, Rohit Mathur7, Samantha P Tippen8, Curtis Gumbs8, Sattva S Neelapu7, Aung Naing9, Linghua Wang8, Adi Diab10, Andrew Futreal8, Roza Nurieva6, Naval Daver4.   

Abstract

Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated with immune checkpoint inhibitors (ICIs) are at risk of pneumonitis as well as pneumonia (combined henceforth as ICI-related pulmonary complications). Little is known about the cellular and molecular mechanisms underlying ICI-related pulmonary complications. We characterized lymphocytes from bronchoalveolar lavage (BAL) fluid and peripheral blood from seven AML/MDS patients with pulmonary symptoms after ICI-based therapy (ICI group) and four ICI-naïve AML/MDS patients with extracellular bacterial or fungal pneumonias (controls). BAL T cells in the ICI group were clonally expanded, and BAL IFNγ+ IL-17- CD8+ T and CXCR3+ CCR6+ Th17/Th1 cells were enriched in the ICI group. Our data suggest that these cells may play a critical role in the pathophysiology of ICI-related pulmonary complications. Understanding of these cell populations may also provide predictive and diagnostic biomarkers of ICI-related pulmonary complications, eventually enabling differentiation of pneumonitis from pneumonia in AML/MDS patients receiving ICI-based therapies.
Copyright © 2021 Kim, Sheshadri, Shannon, Kontoyiannis, Kantarjian, Garcia-Manero, Ravandi, Im, Boddu, Bashoura, Balachandran, Evans, Faiz, Ruiz Vazquez, Divenko, Mathur, Tippen, Gumbs, Neelapu, Naing, Wang, Diab, Futreal, Nurieva and Daver.

Entities:  

Keywords:  Th17/Th1 cells; acute myeloid leukemia; checkpoint inhibitor; immune-related adverse event; pneumonitis

Mesh:

Substances:

Year:  2021        PMID: 33552049      PMCID: PMC7859512          DOI: 10.3389/fimmu.2020.590494

Source DB:  PubMed          Journal:  Front Immunol        ISSN: 1664-3224            Impact factor:   7.561


  33 in total

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