Stem Cell–Derived Dendritic Cells With Radiotherapy Under Study in Preclinical Breast Cancer Models
Posted: Thursday, September 30, 2021
A study conducted by Fumito Ito, MD, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, and colleagues combined local radiotherapy with in situ administration of induced pluripotent stem cells in PD-L1 treatment–resistant mouse tumor models of triple-negative breast cancer and melanoma. According to the researchers, this combination demonstrated antitumor activity in poorly immunogenic and untreated distant tumors, and it also created a tumor microenvironment that may favor the use of anti–PD-L1 therapy. Their results, published in the Journal for ImmunoTherapy of Cancer, suggest there may be therapeutic potential for these stem cell–derived products.
“While our work to develop this strategy is at an early stage and will need to be studied further, we show that these two approaches, radiotherapy and intratumoral induced pluripotent stem cell–dendritic cell administration, can work synergistically to control not only local tumor growth but also distant tumors,” stated Dr. Ito in a Roswell Park press release. “And, we saw evidence of systemic tumor-specific immunological memory, suggesting a potential for long-term tumor control.”
Induced pluripotent stem cells from mice were matured to dendritic cells by seeding them onto OP9 stromal cells that expressed the Notch ligand Delta-like 1. Tumor cells were implanted into mammary glands or injected into either flank of the mice; the animals then underwent intratumor inoculations of stem cell–derived dendritic cells and irradiation.
The combination of dendritic cell administration and radiotherapy not only delayed the growth of radiologically treated and distant tumors, but also promoted the priming of tumor-specific CD8-positive T cells. Radiotherapy appeared to enhance trafficking of these intratumorally injected induced pluripotent stem cell–dendritic cells to tumor-draining lymph nodes, increase the number of dendritic cell/CD8-positive T-cell aggregates, and upregulate CD40 expression. Of note, mice that demonstrated an increase in PD-L1 expression and were injected with the treatment combination and anti–PD-L1 isotype antibody experienced improved tumor growth and survival, leaving immunogenicity virtually unaltered, the authors noted.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.
