Frontiers in Immunology (Jan 2021)

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

  • Sang T. Kim,
  • Ajay Sheshadri,
  • Vickie Shannon,
  • Dimitrios P. Kontoyiannis,
  • Hagop Kantarjian,
  • Guillermo Garcia-Manero,
  • Farhad Ravandi,
  • Jin S. Im,
  • Prajwal Boddu,
  • Lara Bashoura,
  • Diwakar D. Balachandran,
  • Scott E. Evans,
  • Saadia Faiz,
  • Wilfredo Ruiz Vazquez,
  • Margarita Divenko,
  • Rohit Mathur,
  • Samantha P. Tippen,
  • Curtis Gumbs,
  • Sattva S. Neelapu,
  • Aung Naing,
  • Linghua Wang,
  • Adi Diab,
  • Andrew Futreal,
  • Roza Nurieva,
  • Naval Daver

DOI
https://doi.org/10.3389/fimmu.2020.590494
Journal volume & issue
Vol. 11

Abstract

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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.

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