Distinct Role of CD11b+Ly6G−Ly6C− Myeloid-Derived Cells on the Progression of the Primary Tumor and Therapy-Associated Recurrent Brain Tumor

Abstract

Myeloid-derived cells have been implicated as playing essential roles in cancer therapy, particularly in cancer immunotherapy. Most studies have focused on either CD11b+Ly6G+Ly6C+ granulocytic or polymorphonuclear myeloid-derived suppressor cells (G-MDSCs or PMN-MDSCs) or CD11b+Ly6G−Ly6C+ monocytic MDSCs (M-MDSCs), for which clear roles have been established. On the other hand, CD11b+Ly6G−Ly6C− myeloid-derived cells (MDCs) have been less well studied. Here, the CD11b-diphtheria toxin receptor (CD11b-DTR) transgenic mouse model was used to evaluate the role of CD11b+ myeloid-derived cells in chemotherapy for an orthotopic murine astrocytoma, ALTS1C1. Using this transgenic mouse model, two injections of diphtheria toxin (DT) could effectively deplete CD11b+Ly6G−Ly6C− MDCs while leaving CD11b+Ly6G+Ly6C+ PMN-MDSCs and CD11b+Ly6G−Ly6C+ M-MDSCs intact. Depletion of CD11b+Ly6G−Ly6C− MDCs in mice bearing ALTS1C1-tk tumors and receiving ganciclovir (GCV) prolonged the mean survival time for mice from 30.7 to 37.8 days, but not the controls, while the effectiveness of temozolomide was enhanced. Mechanistically, depletion of CD11b+Ly6G−Ly6C− MDCs blunted therapy-induced increases in tumor-associated macrophages (TAMs) and compromised therapy-elicited angiogenesis. Collectively, our findings suggest that CD11b+Ly6G−Ly6C− MDCs could be manipulated to enhance the efficacy of chemotherapy for brain tumors. However, our study also cautions that the timing of any MDC manipulation may be critical to achieve the best therapeutic result.

Microglia-mediated drug resistance by hijacking drug substances from glioma cells

“…[23] We found that these F4/80 + macrophages/microglia were critical in increasing tumor mean vessel density and promoting tumor recurrence following drug treatment. [24] However, it did not distinguish macrophages from microglia in this in vivo model, and the detailed mechanism of how microglia affect brain tumor resistance to chemotherapy is still unclear.…”

“…Cell lines culture Murine astrocytoma cell line, ALTS1C1 (T8239, Applied Biological Materials, Richmond, Canada, or BCRC60582, Hsinchu, Taiwan), and a stable clone of ALTS1C1-Tk was previously established in our lab. [23,24] ALTS1C1-GFP cell line was created by lentiviral infection of GFP-expressing vector into the ALTS1C1 cells, ALTS1C1-GFP-Tk cell line was created by transfection of herpes simplex virus thymidine kinase (HSV-Tk) gene into the ATLS1C1-GFP cell line. UN-KC-6141, a pancreatic adenocarcinoma cell line, was kindly provided by Prof. Surinder K. Batra at the University of Nebraska Medical Center.…”

Chinese Medicine Formula PSORI-CM02 Alleviates Psoriatic Dermatitis via M-MDSCs and Th17 Crosstalk

“…Myeloid-derived cells have been indicated as an essential factor in the immune system, particularly in cancer immunotherapy. Two subtypes of MDSCs have clear roles that have been established in murine: CD11b + Ly6G-Ly6C + monocytic MDSCs (M-MDSCs) and CD11b + Ly6G + Ly6C- polymorphonuclear or granulocytic myeloid-derived suppressor cells (PMN-MDSCs or G-MDSCs) ( Wu and Chiang, 2019 ). Generally, PMN-MDSCs make up the majority of the population of MDSCs.…”

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

“…The former express have the cell surface marker phenotype CD11b + Ly6ClowLy6G + , while the latter are characterized by a CD11b + Ly6ChighLy6Gphenotype. 164,165 Human MDSCs are different from murine MDSCs, which are characterized by no or low expression of HLA-DR and high expression of CD33. Unsurprisingly, the common myeloid biomarker CD11b is also a marker of human MDSCs, and the CD11b and CD33 double-positive HLA-DR-low population can be further classified as M or G MDSCs according to their CD14 or CD15 expression.…”