Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors
- 1Department of Neurology and Neurosurgery, School of Medicine, Johns Hopkins University, United States
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 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, 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: Combination immunotherapy, Myeloid therapy, Glioma, chemotherapy, Radiation, Checkpoint inhibitors, Myeloid-Derived Suppressor Cells (MDSC), Tumor-associated macrophage (TAM)
Received: 26 Apr 2019;
Accepted: 09 Jul 2019.
Edited by:Christian Ostheimer, Martin Luther University of Halle-Wittenberg, Germany
Reviewed by:Carlos Alfaro, NavarraBiomed, Spain
Seon Hee Chang, University of Texas MD Anderson Cancer Center, United States
Copyright: © 2019 Ding, Routkevitch, Jackson and Lim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD. Michael Lim, Department of Neurology and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, 21205, Maryland, United States, firstname.lastname@example.org