Advanced NSCLC patients with high IL-6 levels have altered peripheral T cell population and signaling

Shawn J. Rice, Xin Liu, Jianhong Zhang, Bei Jia, Hong Zheng, Chandra Belani

Research output: Contribution to journalArticle

Abstract

Objectives: High levels of circulating interleukin-6 (IL-6) are associated with a poor prognosis in many types of cancer including non-small cell lung cancer (NSCLC). While the inflammatory cytokine can stimulate the immune system and promote tumor growth, it remains unclear how circulating IL-6 can potentiate a poor prognosis. We hypothesized that a mechanism for IL-6-associated poor prognosis is that these patients would have altered T-cell populations and impaired T-cell signaling. Materials and methods: Plasma levels of IL-6 were measured using a Cytometric Bead Array. T-cell populations from Non-small cell lung cancer patients were characterized using surface markers by flow cytometry, and signaling in the T-cell populations were measured by PhosFlow cytometry. Results: We determine that patients with high circulating IL-6 levels had distinct T cell characteristics relative to those with low levels. Patients with high levels of IL-6 had significantly more T reg cells and elevated Programmed cell death protein-1 (PD-1) expression on CD4 + , CD8 + , Treg, and Th17 cells. These patients also showed impaired signal transducer and activator of transcription-1 (STAT1) signaling upon stimulation with IL-6 and phorbol 12-myristate 13-acetate (PMA), and T-Cells from a healthy donor that were treated for four days with IL-6 displayed a similar muting of STAT signaling, which verified the effect seen in patient samples. Conclusions: This work directly links circulating IL-6 with other poor prognostic indicators, STAT1 and PD-1, and highlights the effects of circulating IL-6 on the immune system. Our data suggest that alteration in T cell populations and function may be a mechanism underlying the poor prognosis seen in NSCLC patients with high IL-6 levels.

Original languageEnglish (US)
Pages (from-to)58-61
Number of pages4
JournalLung Cancer
Volume131
DOIs
StatePublished - May 1 2019

Fingerprint

Non-Small Cell Lung Carcinoma
Interleukin-6
T-Lymphocytes
Population
STAT1 Transcription Factor
Programmed Cell Death 1 Receptor
Immune System
Th17 Cells
Regulatory T-Lymphocytes
Neoplasms
Flow Cytometry
Acetates
Tissue Donors
Cytokines

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

@article{2e3ea35d363943349772ea386cb18bd7,
title = "Advanced NSCLC patients with high IL-6 levels have altered peripheral T cell population and signaling",
abstract = "Objectives: High levels of circulating interleukin-6 (IL-6) are associated with a poor prognosis in many types of cancer including non-small cell lung cancer (NSCLC). While the inflammatory cytokine can stimulate the immune system and promote tumor growth, it remains unclear how circulating IL-6 can potentiate a poor prognosis. We hypothesized that a mechanism for IL-6-associated poor prognosis is that these patients would have altered T-cell populations and impaired T-cell signaling. Materials and methods: Plasma levels of IL-6 were measured using a Cytometric Bead Array. T-cell populations from Non-small cell lung cancer patients were characterized using surface markers by flow cytometry, and signaling in the T-cell populations were measured by PhosFlow cytometry. Results: We determine that patients with high circulating IL-6 levels had distinct T cell characteristics relative to those with low levels. Patients with high levels of IL-6 had significantly more T reg cells and elevated Programmed cell death protein-1 (PD-1) expression on CD4 + , CD8 + , Treg, and Th17 cells. These patients also showed impaired signal transducer and activator of transcription-1 (STAT1) signaling upon stimulation with IL-6 and phorbol 12-myristate 13-acetate (PMA), and T-Cells from a healthy donor that were treated for four days with IL-6 displayed a similar muting of STAT signaling, which verified the effect seen in patient samples. Conclusions: This work directly links circulating IL-6 with other poor prognostic indicators, STAT1 and PD-1, and highlights the effects of circulating IL-6 on the immune system. Our data suggest that alteration in T cell populations and function may be a mechanism underlying the poor prognosis seen in NSCLC patients with high IL-6 levels.",
author = "Rice, {Shawn J.} and Xin Liu and Jianhong Zhang and Bei Jia and Hong Zheng and Chandra Belani",
year = "2019",
month = "5",
day = "1",
doi = "10.1016/j.lungcan.2019.03.014",
language = "English (US)",
volume = "131",
pages = "58--61",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

Advanced NSCLC patients with high IL-6 levels have altered peripheral T cell population and signaling. / Rice, Shawn J.; Liu, Xin; Zhang, Jianhong; Jia, Bei; Zheng, Hong; Belani, Chandra.

In: Lung Cancer, Vol. 131, 01.05.2019, p. 58-61.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Advanced NSCLC patients with high IL-6 levels have altered peripheral T cell population and signaling

AU - Rice, Shawn J.

AU - Liu, Xin

AU - Zhang, Jianhong

AU - Jia, Bei

AU - Zheng, Hong

AU - Belani, Chandra

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Objectives: High levels of circulating interleukin-6 (IL-6) are associated with a poor prognosis in many types of cancer including non-small cell lung cancer (NSCLC). While the inflammatory cytokine can stimulate the immune system and promote tumor growth, it remains unclear how circulating IL-6 can potentiate a poor prognosis. We hypothesized that a mechanism for IL-6-associated poor prognosis is that these patients would have altered T-cell populations and impaired T-cell signaling. Materials and methods: Plasma levels of IL-6 were measured using a Cytometric Bead Array. T-cell populations from Non-small cell lung cancer patients were characterized using surface markers by flow cytometry, and signaling in the T-cell populations were measured by PhosFlow cytometry. Results: We determine that patients with high circulating IL-6 levels had distinct T cell characteristics relative to those with low levels. Patients with high levels of IL-6 had significantly more T reg cells and elevated Programmed cell death protein-1 (PD-1) expression on CD4 + , CD8 + , Treg, and Th17 cells. These patients also showed impaired signal transducer and activator of transcription-1 (STAT1) signaling upon stimulation with IL-6 and phorbol 12-myristate 13-acetate (PMA), and T-Cells from a healthy donor that were treated for four days with IL-6 displayed a similar muting of STAT signaling, which verified the effect seen in patient samples. Conclusions: This work directly links circulating IL-6 with other poor prognostic indicators, STAT1 and PD-1, and highlights the effects of circulating IL-6 on the immune system. Our data suggest that alteration in T cell populations and function may be a mechanism underlying the poor prognosis seen in NSCLC patients with high IL-6 levels.

AB - Objectives: High levels of circulating interleukin-6 (IL-6) are associated with a poor prognosis in many types of cancer including non-small cell lung cancer (NSCLC). While the inflammatory cytokine can stimulate the immune system and promote tumor growth, it remains unclear how circulating IL-6 can potentiate a poor prognosis. We hypothesized that a mechanism for IL-6-associated poor prognosis is that these patients would have altered T-cell populations and impaired T-cell signaling. Materials and methods: Plasma levels of IL-6 were measured using a Cytometric Bead Array. T-cell populations from Non-small cell lung cancer patients were characterized using surface markers by flow cytometry, and signaling in the T-cell populations were measured by PhosFlow cytometry. Results: We determine that patients with high circulating IL-6 levels had distinct T cell characteristics relative to those with low levels. Patients with high levels of IL-6 had significantly more T reg cells and elevated Programmed cell death protein-1 (PD-1) expression on CD4 + , CD8 + , Treg, and Th17 cells. These patients also showed impaired signal transducer and activator of transcription-1 (STAT1) signaling upon stimulation with IL-6 and phorbol 12-myristate 13-acetate (PMA), and T-Cells from a healthy donor that were treated for four days with IL-6 displayed a similar muting of STAT signaling, which verified the effect seen in patient samples. Conclusions: This work directly links circulating IL-6 with other poor prognostic indicators, STAT1 and PD-1, and highlights the effects of circulating IL-6 on the immune system. Our data suggest that alteration in T cell populations and function may be a mechanism underlying the poor prognosis seen in NSCLC patients with high IL-6 levels.

UR - http://www.scopus.com/inward/record.url?scp=85063027904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063027904&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2019.03.014

DO - 10.1016/j.lungcan.2019.03.014

M3 - Article

VL - 131

SP - 58

EP - 61

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -