Anat Stemmer Rachamimov

Massachusetts General Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Robert L. Martuza

Massachusetts General Hospital

Balveen Kaur

Augusta University Health

Ralph Weissleder

Center for Systems Biology

Nico van Rooijen

Vrije Universiteit Amsterdam

Nina Dmitrieva

Immanuel Kant Baltic Federal University

Davide Gianni

AstraZeneca (United Kingdom)

Daniel J. Brat

Northwestern University

Elisabeth J. Fontana

Massachusetts General Hospital

Fred H. Hochberg

Massachusetts General Hospital

Clay B. Marsh

The Ohio State University

Cooperative Institutions

Massachusetts General Hospital

Neurological Surgery

The Ohio State University

Harvard University

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Center for Systems Biology

The Ohio State University Wexner Medical Center

Dana-Farber/Harvard Cancer Center

Johns Hopkins University

Ohio University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Cancer Research (2007)

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Abstract Clinical trials have proven oncolytic virotherapy to be safe but not effective. We have shown that oncolytic viruses (OV) injected into intracranial gliomas established in rodents are rapidly cleared, and this is associated with up-regulation of markers (CD68 and CD163) of cells of monocytic lineage (monocytes/microglia/macrophages). However, it is unclear whether these cells directly impede intratumoral persistence of OV through phagocytosis and whether they infiltrate the tumor from the blood or the brain parenchyma. To investigate this, we depleted phagocytes with clodronate liposomes (CL) in vivo through systemic delivery and ex vivo in brain slice models with gliomas. Interestingly, systemic CL depleted over 80% of peripheral CD163+ macrophages in animal spleen and peripheral blood, thereby decreasing intratumoral infiltration of these cells, but CD68+ cells were unchanged. Intratumoral viral titers increased 5-fold. In contrast, ex vivo CL depleted only CD68+ cells from brain slices, and intratumoral viral titers increased 10-fold. These data indicate that phagocytosis by both peripheral CD163+ and brain-resident CD68+ cells infiltrating tumor directly affects viral clearance from tumor. Thus, improved therapeutic efficacy may require modulation of these innate immune cells. In support of this new therapeutic paradigm, we observed intratumoral up-regulation of CD68+ and CD163+ cells following treatment with OV in a patient with glioblastoma. [Cancer Res 2007;67(19):9398–406]

CD68

Ex vivo

Mononuclear phagocyte system

CD163

Brain tumor

10.1158/0008-5472.can-07-1063

Cite

Citations (163)

Supplementary Figure 1B from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Supplementary Figure 1B from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Brain tumor

10.1158/0008-5472.22371420

Cite

Citations (0)

Supplementary Figure 1A from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Supplementary Figure 1A from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Brain tumor

10.1158/0008-5472.22371423.v1

Cite

Citations (0)

Supplementary Figure 1B from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Supplementary Figure 1B from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Brain tumor

10.1158/0008-5472.22371420.v1

Cite

Citations (0)

Supplementary Figure 4 from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Supplementary Figure 4 from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Brain tumor

10.1158/0008-5472.22371411.v1

Cite

Citations (0)

Supplementary Figure 1A from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Supplementary Figure 1A from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Brain tumor

10.1158/0008-5472.22371423

Cite

Citations (0)

Data from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

<div>AbstractClinical trials have proven oncolytic virotherapy to be safe but not effective. We have shown that oncolytic viruses (OV) injected into intracranial gliomas established in rodents are rapidly cleared, and this is associated with up-regulation of markers (CD68 and CD163) of cells of monocytic lineage (monocytes/microglia/macrophages). However, it is unclear whether these cells directly impede intratumoral persistence of OV through phagocytosis and whether they infiltrate the tumor from the blood or the brain parenchyma. To investigate this, we depleted phagocytes with clodronate liposomes (CL) in vivo through systemic delivery and ex vivo in brain slice models with gliomas. Interestingly, systemic CL depleted over 80% of peripheral CD163+ macrophages in animal spleen and peripheral blood, thereby decreasing intratumoral infiltration of these cells, but CD68+ cells were unchanged. Intratumoral viral titers increased 5-fold. In contrast, ex vivo CL depleted only CD68+ cells from brain slices, and intratumoral viral titers increased 10-fold. These data indicate that phagocytosis by both peripheral CD163+ and brain-resident CD68+ cells infiltrating tumor directly affects viral clearance from tumor. Thus, improved therapeutic efficacy may require modulation of these innate immune cells. In support of this new therapeutic paradigm, we observed intratumoral up-regulation of CD68+ and CD163+ cells following treatment with OV in a patient with glioblastoma. [Cancer Res 2007;67(19):9398–406]</div>

Brain tumor

10.1158/0008-5472.c.6496785.v1

Cite

Citations (0)

Supplementary Figure 4 from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Giulia Fulci Nina Dmitrieva Davide Gianni Elisabeth J. Fontana Xiaogang Pan

Supplementary Figure 4 from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses

Brain tumor

10.1158/0008-5472.22371411

Cite

Citations (0)

Supplementary Figure 3 from Depletion of Peripheral Macrophages and Brain Microglia Increases Brain Tumor Titers of Oncolytic Viruses