Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors

Andy S. Ding, Denis Routkevitch, Christina Jackson, Michael Lim

Research output: Contribution to journalReview article

Abstract

Myeloid cells constitute a significant part of the immune system in the context of cancer, exhibiting both immunostimulatory effects, through their role as antigen presenting cells, and immunosuppressive effects, through their polarization to myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. While they are rarely sufficient to generate potent anti-tumor effects on their own, myeloid cells have the ability to interact with a variety of immune populations to aid in mounting an appropriate anti-tumor immune response. Therefore, myeloid therapies have gained momentum as a potential adjunct to current therapies such as immune checkpoint inhibitors (ICIs), dendritic cell vaccines, oncolytic viruses, and traditional chemoradiation to enhance therapeutic response. In this review, we outline critical pathways involved in the recruitment of the myeloid population to the tumor microenvironment and in their polarization to immunostimulatory or immunosuppressive phenotypes. We also emphasize existing strategies of modulating myeloid recruitment and polarization to improve anti-tumor immune responses. We then summarize current preclinical and clinical studies that highlight treatment outcomes of combining myeloid targeted therapies with other immune-based and traditional therapies. Despite promising results from reports of limited clinical trials thus far, there remain challenges in optimally harnessing the myeloid compartment as an adjunct to enhancing anti-tumor immune responses. Further large Phase II and ultimately Phase III clinical trials are needed to elucidate the treatment benefit of combination therapies in the fight against cancer.

Original languageEnglish (US)
Number of pages1
JournalFrontiers in immunology
Volume10
DOIs
StatePublished - Jan 1 2019

Fingerprint

Myeloid Cells
Glioma
Neoplasms
Immunosuppressive Agents
Therapeutics
Oncolytic Viruses
Phase III Clinical Trials
Critical Pathways
Tumor Microenvironment
Antigen-Presenting Cells
Dendritic Cells
Population
Immune System
Vaccines
Macrophages
Clinical Trials
Phenotype

Keywords

  • checkpoint inhibitors
  • chemotherapy
  • combination immunotherapy
  • glioma
  • myeloid therapy
  • myeloid-derived suppressor cells
  • radiation
  • tumor-associated macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors. / Ding, Andy S.; Routkevitch, Denis; Jackson, Christina; Lim, Michael.

In: Frontiers in immunology, Vol. 10, 01.01.2019.

Research output: Contribution to journalReview article

Ding, Andy S. ; Routkevitch, Denis ; Jackson, Christina ; Lim, Michael. / Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors. In: Frontiers in immunology. 2019 ; Vol. 10.
@article{a8274f4ef01147e5aabe35e3b63a023e,
title = "Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors",
abstract = "Myeloid cells constitute a significant part of the immune system in the context of cancer, exhibiting both immunostimulatory effects, through their role as antigen presenting cells, and immunosuppressive effects, through their polarization to myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. While they are rarely sufficient to generate potent anti-tumor effects on their own, myeloid cells have the ability to interact with a variety of immune populations to aid in mounting an appropriate anti-tumor immune response. Therefore, myeloid therapies have gained momentum as a potential adjunct to current therapies such as immune checkpoint inhibitors (ICIs), dendritic cell vaccines, oncolytic viruses, and traditional chemoradiation to enhance therapeutic response. In this review, we outline critical pathways involved in the recruitment of the myeloid population to the tumor microenvironment and in their polarization to immunostimulatory or immunosuppressive phenotypes. We also emphasize existing strategies of modulating myeloid recruitment and polarization to improve anti-tumor immune responses. We then summarize current preclinical and clinical studies that highlight treatment outcomes of combining myeloid targeted therapies with other immune-based and traditional therapies. Despite promising results from reports of limited clinical trials thus far, there remain challenges in optimally harnessing the myeloid compartment as an adjunct to enhancing anti-tumor immune responses. Further large Phase II and ultimately Phase III clinical trials are needed to elucidate the treatment benefit of combination therapies in the fight against cancer.",
keywords = "checkpoint inhibitors, chemotherapy, combination immunotherapy, glioma, myeloid therapy, myeloid-derived suppressor cells, radiation, tumor-associated macrophages",
author = "Ding, {Andy S.} and Denis Routkevitch and Christina Jackson and Michael Lim",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fimmu.2019.01715",
language = "English (US)",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors

AU - Ding, Andy S.

AU - Routkevitch, Denis

AU - Jackson, Christina

AU - Lim, Michael

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Myeloid cells constitute a significant part of the immune system in the context of cancer, exhibiting both immunostimulatory effects, through their role as antigen presenting cells, and immunosuppressive effects, through their polarization to myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. While they are rarely sufficient to generate potent anti-tumor effects on their own, myeloid cells have the ability to interact with a variety of immune populations to aid in mounting an appropriate anti-tumor immune response. Therefore, myeloid therapies have gained momentum as a potential adjunct to current therapies such as immune checkpoint inhibitors (ICIs), dendritic cell vaccines, oncolytic viruses, and traditional chemoradiation to enhance therapeutic response. In this review, we outline critical pathways involved in the recruitment of the myeloid population to the tumor microenvironment and in their polarization to immunostimulatory or immunosuppressive phenotypes. We also emphasize existing strategies of modulating myeloid recruitment and polarization to improve anti-tumor immune responses. We then summarize current preclinical and clinical studies that highlight treatment outcomes of combining myeloid targeted therapies with other immune-based and traditional therapies. Despite promising results from reports of limited clinical trials thus far, there remain challenges in optimally harnessing the myeloid compartment as an adjunct to enhancing anti-tumor immune responses. Further large Phase II and ultimately Phase III clinical trials are needed to elucidate the treatment benefit of combination therapies in the fight against cancer.

AB - Myeloid cells constitute a significant part of the immune system in the context of cancer, exhibiting both immunostimulatory effects, through their role as antigen presenting cells, and immunosuppressive effects, through their polarization to myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. While they are rarely sufficient to generate potent anti-tumor effects on their own, myeloid cells have the ability to interact with a variety of immune populations to aid in mounting an appropriate anti-tumor immune response. Therefore, myeloid therapies have gained momentum as a potential adjunct to current therapies such as immune checkpoint inhibitors (ICIs), dendritic cell vaccines, oncolytic viruses, and traditional chemoradiation to enhance therapeutic response. In this review, we outline critical pathways involved in the recruitment of the myeloid population to the tumor microenvironment and in their polarization to immunostimulatory or immunosuppressive phenotypes. We also emphasize existing strategies of modulating myeloid recruitment and polarization to improve anti-tumor immune responses. We then summarize current preclinical and clinical studies that highlight treatment outcomes of combining myeloid targeted therapies with other immune-based and traditional therapies. Despite promising results from reports of limited clinical trials thus far, there remain challenges in optimally harnessing the myeloid compartment as an adjunct to enhancing anti-tumor immune responses. Further large Phase II and ultimately Phase III clinical trials are needed to elucidate the treatment benefit of combination therapies in the fight against cancer.

KW - checkpoint inhibitors

KW - chemotherapy

KW - combination immunotherapy

KW - glioma

KW - myeloid therapy

KW - myeloid-derived suppressor cells

KW - radiation

KW - tumor-associated macrophages

UR - http://www.scopus.com/inward/record.url?scp=85071281658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071281658&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2019.01715

DO - 10.3389/fimmu.2019.01715

M3 - Review article

C2 - 31396227

AN - SCOPUS:85071281658

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -