Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

Jennifer Cao; Lyndah Chow; Steven Dow

doi:10.3389/fonc.2023.1116016

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

Front Oncol. 2023 Apr 11:13:1116016. doi: 10.3389/fonc.2023.1116016. eCollection 2023.

Authors

Jennifer Cao^{1

2}, Lyndah Chow^{1

3}, Steven Dow^{1

2

3}

Affiliations

¹ Flint Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
² Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
³ Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.

Abstract

Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers current strategies targeting myeloid suppressor cells in the TME to enhance anti-tumoral immunity, including strategies that target chemokine receptors to deplete selected immune suppressive myeloid cells and relieve the inhibition imposed on the effector arms of adaptive immunity. Remodeling the TME can in turn improve the activity of other immunotherapies such as checkpoint blockade and adoptive T cell therapies in immunologically "cold" tumors. When possible, in this review, we have provided evidence and outcomes from recent or current clinical trials evaluating the effectiveness of the specific strategies used to target myeloid cells in the TME. The review seeks to provide a broad overview of how myeloid cell targeting can become a key foundational approach to an overall strategy for improving tumor responses to immunotherapy.

Keywords: cancer; cancer immune therapy; dendritc cells; immune suppresion; myeloid derived suppressor cells (MDSC); tumor associate macrophages (TAM); tumor associated neutrophils (TAN); tumor microenvironment.

Publication types

Review

Grants and funding

This work was supported by the Charles Shipley Family Foundation, The V Foundation grant DCORC2021-003 awarded to JC and SD and NIH 1U01CA224182-01 awarded to SD.