Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy

Abstract

Therapeutic approaches that engage immune cells to treat cancer are becoming increasingly utilized in the clinics and demonstrated durable clinical benefit in several solid tumor types. Most of the current immunotherapies focus on manipulating T cells, however, the tumor microenvironment (TME) is abundantly infiltrated by a heterogeneous population of tumor-associated myeloid cells, including tumor-associated macrophages (TAMs), tumor-associated dendritic cells (TADCs), tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). Educated by signals perceived in the TME, these cells often acquire tumor-promoting properties ultimately favoring disease progression. Upon appropriate stimuli, myeloid cells can exhibit cytoxic, phagocytic, and antigen-presenting activities thereby bolstering antitumor immune responses. Thus, depletion, reprogramming or reactivation of myeloid cells to either directly eradicate malignant cells or promote antitumor T-cell responses is an emerging field of interest. In this review, we briefly discuss the tumor-promoting and tumor-suppressive roles of myeloid cells in the TME, and describe potential therapeutic strategies in preclinical and clinical development that aim to target them to further expand the range of current treatment options.

Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients

“…We then proceeded to calculate the scores for other populations of immune cells, including myeloid cells, known to contribute to T-cell suppression ( 18 – 20 ). We found a significant increase in the score of mast cells ( p = 0.02) in AA tumors when compared to CA ( Figure 7D ).…”

“…We found a significant increase in the score of mast cells ( p = 0.02) in AA tumors when compared to CA ( Figure 7D ). These cells are associated with colon tumor growth and chronic inflammation ( 18 – 20 ). In addition, although there were not significant differences among the scores of dendritic cells, macrophages, neutrophils or B cells, they appeared to be upregulated in AAs when compared to the CA group ( Supplementary Figure 4 ).…”

Role of osteopontin in dendritic cell shaping of immune responses

“…In the tumor microenvironment OPN can be produced by neoplastic cells as well as by infiltrating immune cells, including DCs, tumor-associated macrophages (TAMs) and Myeloid-Derived Suppressor Cells (MDSCs) [100][101][102]. Several studies show that OPN creates a protumorigenic microenvironment by different mechanisms.…”

Autophagy, the innate immune response and cancer

“…In an irradiated glioblastoma model, NF-jB signalling in glioblastoma cells caused the recruitment of Ly6G + inflammatory cells, which facilitated the conversion of glioblastoma cells to glioblastoma stem cells [38]. In tumours, Ly6G + inflammatory cells can include granulocytic myeloidderived suppressor cells and tumour-associated neutrophils, which can secrete factors to promote tumour growth [39,40]. Additionally, the IL-6/STAT3 signalling axis has been shown to play a role in colorectal cancer cell stemness via FRA1 deacetylation [41].…”