Figure 1. Luc Reporter Cell Line-B16F10 was used by the researchers to show how gene expression analysis using qRT-PCR, western blotting, luciferase assays, and Matrigel invasion assays evaluate the effect of Shh signaling inhibition on melanoma invasion. (Gunarta IK, et al., 2017)
Induction of Trained Immunity Inhibits Tumor Growth
Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity
Paper
2020
Cell |
DOI
Background
This study shows that β-glucan-induced trained innate immunity suppresses tumor growth in mice. Pre-treatment with β-glucan reprogrammed granulopoiesis and neutrophils toward an anti-tumor phenotype, independent of adaptive immunity. Trained neutrophils limited tumor growth in a ROS-dependent manner, and the effect required type I interferon signaling. Bone marrow transplantation transmitted anti-tumor trained granulopoiesis to naive recipients, and systemic transfer of trained neutrophils inhibited established tumors. These findings identify innate immune training of granulopoiesis as a potential cancer immunotherapy strategy.
Key Findings
β-glucan-induced trained immunity significantly diminished B16-F10 melanoma and Lewis lung carcinoma growth in wild-type and Rag1−/− mice, indicating independence from adaptive immunity. Trained immunity did not alter intratumoral immune cell frequencies but reprogrammed tumor-associated neutrophils (TANs) toward an anti-tumor TAN1-like transcriptomic phenotype, with enhanced phagocytosis, antigen presentation, ROS pathway, and EIF2/eIF4/p70S6K signaling. Splenic neutrophils from β-glucan-trained mice displayed enhanced ROS-dependent tumor cytotoxicity; NCF1 deficiency abolished their anti-tumor activity in adoptive transfer. Training also rewired bone marrow granulocyte-monocyte progenitors, with type I IFN signaling and epigenetic changes, and was transmissible by bone marrow transplantation. Systemic administration of trained neutrophils inhibited established tumor growth, supporting trained granulopoiesis as a cancer immunotherapy approach.
Contribution
Creative Biogene provided the B16-F10-Luc melanoma cell line (Cat#CSC-RR0234), a luciferase-expressing reporter used in neutrophil co-culture cytotoxicity assays and adoptive transfer experiments. This reagent enabled luminescence-based quantification of tumor cell survival and helped establish ROS-dependent anti-tumor activity of trained neutrophils.
This study shows that β-glucan-induced trained innate immunity suppresses tumor growth in mice. Pre-treatment with β-glucan reprogrammed granulopoiesis and neutrophils toward an anti-tumor phenotype, independent of adaptive immunity. Trained neutrophils limited tumor growth in a ROS-dependent manner, and the effect required type I interferon signaling. Bone marrow transplantation transmitted anti-tumor trained granulopoiesis to naive recipients, and systemic transfer of trained neutrophils inhibited established tumors. These findings identify innate immune training of granulopoiesis as a potential cancer immunotherapy strategy.
Key Findings
β-glucan-induced trained immunity significantly diminished B16-F10 melanoma and Lewis lung carcinoma growth in wild-type and Rag1−/− mice, indicating independence from adaptive immunity. Trained immunity did not alter intratumoral immune cell frequencies but reprogrammed tumor-associated neutrophils (TANs) toward an anti-tumor TAN1-like transcriptomic phenotype, with enhanced phagocytosis, antigen presentation, ROS pathway, and EIF2/eIF4/p70S6K signaling. Splenic neutrophils from β-glucan-trained mice displayed enhanced ROS-dependent tumor cytotoxicity; NCF1 deficiency abolished their anti-tumor activity in adoptive transfer. Training also rewired bone marrow granulocyte-monocyte progenitors, with type I IFN signaling and epigenetic changes, and was transmissible by bone marrow transplantation. Systemic administration of trained neutrophils inhibited established tumor growth, supporting trained granulopoiesis as a cancer immunotherapy approach.
Contribution
Creative Biogene provided the B16-F10-Luc melanoma cell line (Cat#CSC-RR0234), a luciferase-expressing reporter used in neutrophil co-culture cytotoxicity assays and adoptive transfer experiments. This reagent enabled luminescence-based quantification of tumor cell survival and helped establish ROS-dependent anti-tumor activity of trained neutrophils.