Lin - CCR2 + hematopoietic stem and progenitor cells overcome resistance to PD-1 blockade.

Autor: Flores CT; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA. catherine.flores@neurosurgery.ufl.edu., Wildes TJ; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA., Drake JA; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA., Moore GL; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA., Dean BD; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA., Abraham RS; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA., Mitchell DA; University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, 1149S Newell Dr, L2-100, Gainesville, FL, 32611, USA. duane.mitchell@neurosurgery.ufl.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Oct 17; Vol. 9 (1), pp. 4313. Date of Electronic Publication: 2018 Oct 17.
DOI: 10.1038/s41467-018-06182-5
Abstrakt: Immune checkpoint blockade using anti-PD-1 monoclonal antibodies has shown considerable promise in the treatment of solid tumors, but brain tumors remain notoriously refractory to treatment. In CNS malignancies that are completely resistant to PD-1 blockade, we found that bone marrow-derived, lineage-negative hematopoietic stem and progenitor cells (HSCs) that express C-C chemokine receptor type 2 (CCR2 + ) reverses treatment resistance and sensitizes mice to curative immunotherapy. HSC transfer with PD-1 blockade increases T-cell frequency and activation within tumors in preclinical models of glioblastoma and medulloblastoma. CCR2 + HSCs preferentially migrate to intracranial brain tumors and differentiate into antigen-presenting cells within the tumor microenvironment and cross-present tumor-derived antigens to CD8 + T cells. HSC transfer also rescues tumor resistance to adoptive cellular therapy in medulloblastoma and glioblastoma. Our studies demonstrate a novel role for CCR2 + HSCs in overcoming brain tumor resistance to PD-1 checkpoint blockade and adoptive cellular therapy in multiple invasive brain tumor models.
Databáze: MEDLINE
Externí odkaz: