Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study

Vivek Murthy, Daniel P. Katzman, Jun Chieh J. Tsay, Jamie L. Bessich, Gaetane C. Michaud, Samaan Rafeq, Janna Minehart, Keshav Mangalick, M. A.Curotto de Lafaille, Chandra Goparaju, Harvey Pass, Daniel H. Sterman

Research output: Contribution to journalArticle

Abstract

Objectives: Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment. In this study, we compared the immunophenotype from different sites within individuals to primary tumor characteristics in patients with NSCLC to see whether there were tumor-regional differences in immunophenotype which could be evaluated from transbronchial needle aspirates. Materials and Methods: Twenty patients were enrolled in this study and had tissue (lymph node aspirates and/or peripheral blood) obtained during standard of care bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis or staging of known or suspected NSCLC. Aspirates and blood underwent flow-assisted cell sorting and a subset of sorted effector T cells underwent RNA quantitation to determine feasibility of this approach. Immunophenotypic patterns from twelve patients with paired data from tumor-draining and non-tumor draining lymph nodes (NDLN) were compared relative to one another and based on PD-L1 immunohistochemistry and primary tumor histology. Results: TDLN had significantly fewer CD4+ T cells (12.68% vs 27%, p = 0.002) and significantly more regulatory T cells (Treg, 12.03% vs 9.52%, p = 0.03) relative to paired NDLN suggesting tumor-regional immunosuppression. There were significantly more Treg in NDLN relative to paired PBMC (9.52% vs 5.6%, p = 0.016). Patients with PD-L1 expression ≥50% had significantly greater tumor-regional CD4+ T cell depletion compared to patients with PD-L1 expression <50% (−35.98% vs −1.89%, p = 0.0357; negative values represent absolute difference between paired TDLN and NDLN). Conclusions: In patients with NSCLC, TDLN have a suppressive immunophenotype correlating with tumor PD-L1 status and can be assessed during routine EBUS-TBNA.

Original languageEnglish (US)
Pages (from-to)94-99
Number of pages6
JournalLung Cancer
Volume137
DOIs
StatePublished - Nov 2019

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Non-Small Cell Lung Carcinoma
Needles
Lymph Nodes
Neoplasms
T-Lymphocytes
Standard of Care
Tumor Microenvironment
Bronchoscopy
Regulatory T-Lymphocytes
Immunosuppression
Immunity
Histology
Immunohistochemistry
RNA

Keywords

  • Bronchoscopy
  • EBUS
  • Endobronchial ultrasound
  • Interventional pulmonology
  • Lung cancer
  • Lymph node
  • NSCLC
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration : A pilot study. / Murthy, Vivek; Katzman, Daniel P.; Tsay, Jun Chieh J.; Bessich, Jamie L.; Michaud, Gaetane C.; Rafeq, Samaan; Minehart, Janna; Mangalick, Keshav; de Lafaille, M. A.Curotto; Goparaju, Chandra; Pass, Harvey; Sterman, Daniel H.

In: Lung Cancer, Vol. 137, 11.2019, p. 94-99.

Research output: Contribution to journalArticle

Murthy, Vivek ; Katzman, Daniel P. ; Tsay, Jun Chieh J. ; Bessich, Jamie L. ; Michaud, Gaetane C. ; Rafeq, Samaan ; Minehart, Janna ; Mangalick, Keshav ; de Lafaille, M. A.Curotto ; Goparaju, Chandra ; Pass, Harvey ; Sterman, Daniel H. / Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration : A pilot study. In: Lung Cancer. 2019 ; Vol. 137. pp. 94-99.
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title = "Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study",
abstract = "Objectives: Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment. In this study, we compared the immunophenotype from different sites within individuals to primary tumor characteristics in patients with NSCLC to see whether there were tumor-regional differences in immunophenotype which could be evaluated from transbronchial needle aspirates. Materials and Methods: Twenty patients were enrolled in this study and had tissue (lymph node aspirates and/or peripheral blood) obtained during standard of care bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis or staging of known or suspected NSCLC. Aspirates and blood underwent flow-assisted cell sorting and a subset of sorted effector T cells underwent RNA quantitation to determine feasibility of this approach. Immunophenotypic patterns from twelve patients with paired data from tumor-draining and non-tumor draining lymph nodes (NDLN) were compared relative to one another and based on PD-L1 immunohistochemistry and primary tumor histology. Results: TDLN had significantly fewer CD4+ T cells (12.68{\%} vs 27{\%}, p = 0.002) and significantly more regulatory T cells (Treg, 12.03{\%} vs 9.52{\%}, p = 0.03) relative to paired NDLN suggesting tumor-regional immunosuppression. There were significantly more Treg in NDLN relative to paired PBMC (9.52{\%} vs 5.6{\%}, p = 0.016). Patients with PD-L1 expression ≥50{\%} had significantly greater tumor-regional CD4+ T cell depletion compared to patients with PD-L1 expression <50{\%} (−35.98{\%} vs −1.89{\%}, p = 0.0357; negative values represent absolute difference between paired TDLN and NDLN). Conclusions: In patients with NSCLC, TDLN have a suppressive immunophenotype correlating with tumor PD-L1 status and can be assessed during routine EBUS-TBNA.",
keywords = "Bronchoscopy, EBUS, Endobronchial ultrasound, Interventional pulmonology, Lung cancer, Lymph node, NSCLC, PD-L1",
author = "Vivek Murthy and Katzman, {Daniel P.} and Tsay, {Jun Chieh J.} and Bessich, {Jamie L.} and Michaud, {Gaetane C.} and Samaan Rafeq and Janna Minehart and Keshav Mangalick and {de Lafaille}, {M. A.Curotto} and Chandra Goparaju and Harvey Pass and Sterman, {Daniel H.}",
year = "2019",
month = "11",
doi = "10.1016/j.lungcan.2019.08.008",
language = "English (US)",
volume = "137",
pages = "94--99",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration

T2 - A pilot study

AU - Murthy, Vivek

AU - Katzman, Daniel P.

AU - Tsay, Jun Chieh J.

AU - Bessich, Jamie L.

AU - Michaud, Gaetane C.

AU - Rafeq, Samaan

AU - Minehart, Janna

AU - Mangalick, Keshav

AU - de Lafaille, M. A.Curotto

AU - Goparaju, Chandra

AU - Pass, Harvey

AU - Sterman, Daniel H.

PY - 2019/11

Y1 - 2019/11

N2 - Objectives: Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment. In this study, we compared the immunophenotype from different sites within individuals to primary tumor characteristics in patients with NSCLC to see whether there were tumor-regional differences in immunophenotype which could be evaluated from transbronchial needle aspirates. Materials and Methods: Twenty patients were enrolled in this study and had tissue (lymph node aspirates and/or peripheral blood) obtained during standard of care bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis or staging of known or suspected NSCLC. Aspirates and blood underwent flow-assisted cell sorting and a subset of sorted effector T cells underwent RNA quantitation to determine feasibility of this approach. Immunophenotypic patterns from twelve patients with paired data from tumor-draining and non-tumor draining lymph nodes (NDLN) were compared relative to one another and based on PD-L1 immunohistochemistry and primary tumor histology. Results: TDLN had significantly fewer CD4+ T cells (12.68% vs 27%, p = 0.002) and significantly more regulatory T cells (Treg, 12.03% vs 9.52%, p = 0.03) relative to paired NDLN suggesting tumor-regional immunosuppression. There were significantly more Treg in NDLN relative to paired PBMC (9.52% vs 5.6%, p = 0.016). Patients with PD-L1 expression ≥50% had significantly greater tumor-regional CD4+ T cell depletion compared to patients with PD-L1 expression <50% (−35.98% vs −1.89%, p = 0.0357; negative values represent absolute difference between paired TDLN and NDLN). Conclusions: In patients with NSCLC, TDLN have a suppressive immunophenotype correlating with tumor PD-L1 status and can be assessed during routine EBUS-TBNA.

AB - Objectives: Tumor draining lymph nodes (TDLN) are key sites of early immunoediting in patients with non-small cell lung cancer (NSCLC) and play an important role in generating anti-tumor immunity. Immune suppression in the tumor microenvironment has prognostic implications and may predict therapeutic response. T cell composition of draining lymph nodes may reflect an immunophenotype with similar prognostic potential which could be measured during standard-of-care bronchoscopic assessment. In this study, we compared the immunophenotype from different sites within individuals to primary tumor characteristics in patients with NSCLC to see whether there were tumor-regional differences in immunophenotype which could be evaluated from transbronchial needle aspirates. Materials and Methods: Twenty patients were enrolled in this study and had tissue (lymph node aspirates and/or peripheral blood) obtained during standard of care bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis or staging of known or suspected NSCLC. Aspirates and blood underwent flow-assisted cell sorting and a subset of sorted effector T cells underwent RNA quantitation to determine feasibility of this approach. Immunophenotypic patterns from twelve patients with paired data from tumor-draining and non-tumor draining lymph nodes (NDLN) were compared relative to one another and based on PD-L1 immunohistochemistry and primary tumor histology. Results: TDLN had significantly fewer CD4+ T cells (12.68% vs 27%, p = 0.002) and significantly more regulatory T cells (Treg, 12.03% vs 9.52%, p = 0.03) relative to paired NDLN suggesting tumor-regional immunosuppression. There were significantly more Treg in NDLN relative to paired PBMC (9.52% vs 5.6%, p = 0.016). Patients with PD-L1 expression ≥50% had significantly greater tumor-regional CD4+ T cell depletion compared to patients with PD-L1 expression <50% (−35.98% vs −1.89%, p = 0.0357; negative values represent absolute difference between paired TDLN and NDLN). Conclusions: In patients with NSCLC, TDLN have a suppressive immunophenotype correlating with tumor PD-L1 status and can be assessed during routine EBUS-TBNA.

KW - Bronchoscopy

KW - EBUS

KW - Endobronchial ultrasound

KW - Interventional pulmonology

KW - Lung cancer

KW - Lymph node

KW - NSCLC

KW - PD-L1

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U2 - 10.1016/j.lungcan.2019.08.008

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M3 - Article

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AN - SCOPUS:85072599617

VL - 137

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JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

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