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:10.3389/fimmu.2020.590494

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 NaingLinghua Wang, Adi Diab, Andrew Futreal, Roza Nurieva, Naval Daver

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English (US)
Article number	590494
Journal	Frontiers in immunology
Volume	11
DOIs	https://doi.org/10.3389/fimmu.2020.590494
State	Published - Jan 21 2021

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility
Clinical and Translational Research Center

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10.3389/fimmu.2020.590494

Cite this

Kim, S. T., Sheshadri, A., Shannon, V., Kontoyiannis, D. P., Kantarjian, H., Garcia-Manero, G., Ravandi, F., Im, J. S., Boddu, P., Bashoura, L., Balachandran, D. D., Evans, S. E., Faiz, S., Ruiz Vazquez, W., Divenko, M., Mathur, R., Tippen, S. P., Gumbs, C., Neelapu, S. S., ... Daver, N. (2021). Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications. Frontiers in immunology, 11, Article 590494. https://doi.org/10.3389/fimmu.2020.590494

Kim, ST, Sheshadri, A , Shannon, V , Kontoyiannis, DP , Kantarjian, H , Garcia-Manero, G , Ravandi, F , Im, JS, Boddu, P, Bashoura, L , Balachandran, DD , Evans, SE , Faiz, S, Ruiz Vazquez, W, Divenko, M, Mathur, R, Tippen, SP, Gumbs, C, Neelapu, SS , Naing, A , Wang, L , Diab, A , Futreal, A , Nurieva, R & Daver, N 2021, 'Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications', Frontiers in immunology, vol. 11, 590494. https://doi.org/10.3389/fimmu.2020.590494

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

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-na{\"i}ve 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.",

keywords = "Th17/Th1 cells, acute myeloid leukemia, checkpoint inhibitor, immune-related adverse event, pneumonitis",

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

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 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.",

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AU - Sheshadri, Ajay

AU - Shannon, Vickie

AU - Kontoyiannis, Dimitrios P.

AU - Kantarjian, Hagop

AU - Garcia-Manero, Guillermo

AU - Ravandi, Farhad

AU - Im, Jin S.

AU - Boddu, Prajwal

AU - Bashoura, Lara

AU - Balachandran, Diwakar D.

AU - Evans, Scott E.

AU - Faiz, Saadia

AU - Ruiz Vazquez, Wilfredo

AU - Divenko, Margarita

AU - Mathur, Rohit

AU - Tippen, Samantha P.

AU - Gumbs, Curtis

AU - Neelapu, Sattva S.

AU - Naing, Aung

AU - Wang, Linghua

AU - Diab, Adi

AU - Futreal, Andrew

AU - Nurieva, Roza

AU - Daver, Naval

N1 - Publisher Copyright: © 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.

PY - 2021/1/21

Y1 - 2021/1/21

N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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