Myeloid cells in circulation and tumor microenvironment of breast cancer patients

Muhammd Toor, Azharuddin Sajid Syed Khaja, Haytham El Salhat, Issam Faour, Jihad Kanbar, Asif A. Quadri, Mohamed Albashir, Eyad Elkord

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalCancer Immunology, Immunotherapy
DOIs
Publication statusAccepted/In press - 10 Mar 2017

Fingerprint

Tumor Microenvironment
Myeloid Cells
Breast Neoplasms
Immunosuppressive Agents
Granulocytes
Neoplasms
Arginase
Blood Donors
Monocytes
Breast
T-Lymphocytes
Phenotype
Myeloid-Derived Suppressor Cells

Keywords

  • Breast cancer
  • Circulation
  • Myeloid cells
  • Myeloid-derived suppressor cells
  • Neutrophils
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Myeloid cells in circulation and tumor microenvironment of breast cancer patients. / Toor, Muhammd; Syed Khaja, Azharuddin Sajid; El Salhat, Haytham; Faour, Issam; Kanbar, Jihad; Quadri, Asif A.; Albashir, Mohamed; Elkord, Eyad.

In: Cancer Immunology, Immunotherapy, 10.03.2017, p. 1-12.

Research output: Contribution to journalArticle

Toor, Muhammd ; Syed Khaja, Azharuddin Sajid ; El Salhat, Haytham ; Faour, Issam ; Kanbar, Jihad ; Quadri, Asif A. ; Albashir, Mohamed ; Elkord, Eyad. / Myeloid cells in circulation and tumor microenvironment of breast cancer patients. In: Cancer Immunology, Immunotherapy. 2017 ; pp. 1-12.
@article{1b111732a605478487822a33baa9b460,
title = "Myeloid cells in circulation and tumor microenvironment of breast cancer patients",
abstract = "Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.",
keywords = "Breast cancer, Circulation, Myeloid cells, Myeloid-derived suppressor cells, Neutrophils, Tumor microenvironment",
author = "Muhammd Toor and {Syed Khaja}, {Azharuddin Sajid} and {El Salhat}, Haytham and Issam Faour and Jihad Kanbar and Quadri, {Asif A.} and Mohamed Albashir and Eyad Elkord",
year = "2017",
month = "3",
day = "10",
doi = "10.1007/s00262-017-1977-z",
language = "English",
pages = "1--12",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",

}

TY - JOUR

T1 - Myeloid cells in circulation and tumor microenvironment of breast cancer patients

AU - Toor, Muhammd

AU - Syed Khaja, Azharuddin Sajid

AU - El Salhat, Haytham

AU - Faour, Issam

AU - Kanbar, Jihad

AU - Quadri, Asif A.

AU - Albashir, Mohamed

AU - Elkord, Eyad

PY - 2017/3/10

Y1 - 2017/3/10

N2 - Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.

AB - Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.

KW - Breast cancer

KW - Circulation

KW - Myeloid cells

KW - Myeloid-derived suppressor cells

KW - Neutrophils

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85014749898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014749898&partnerID=8YFLogxK

U2 - 10.1007/s00262-017-1977-z

DO - 10.1007/s00262-017-1977-z

M3 - Article

C2 - 28283696

AN - SCOPUS:85014749898

SP - 1

EP - 12

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

ER -