Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

@article{Guerriero2017ClassIH,
  title={Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages},
  author={Jennifer L. Guerriero and Alaba Sotayo and Holly E. Ponichtera and Jessica A. Castrillon and Alexandra L. Pourzia and Sara E Schad and Shawn F. Johnson and Ruben D Carrasco and Suzan Lazo and Roderick T Bronson and Scott P. Davis and Mercedes Lobera and Michael A. Nolan and Anthony G. Letai},
  journal={Nature},
  year={2017},
  volume={543},
  pages={428-432}
}
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate… 

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References

SHOWING 1-10 OF 35 REFERENCES

CSF-1R inhibition alters macrophage polarization and blocks glioma progression

The results identify TAMs as a promising therapeutic target for proneural gliomas and establish the translational potential of CSF-1R inhibition for GBM.

Therapeutic Peptide Vaccine-Induced CD8 T Cells Strongly Modulate Intratumoral Macrophages Required for Tumor Regression

Treatment of cervical carcinoma in mouse models with synthetic long peptide (SLP) vaccines induced influx of cytokine-producing CD8 T cells that strongly altered the numbers and phenotype of intratumoral macrophages, showing that therapeutic peptide vaccination could induce cytokin-producing T cells with strong macrophage-skewing capacity necessary for tumor shrinkage.

Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment

This study examined whether neutralizing CD11b monoclonal antibodies could inhibit the recruitment of myeloid cells into irradiated tumors and inhibit their regrowth and supported the rationale of using clinically available Mac-1 (CD11b/CD18) antibodies as an adjuvant therapy to radiotherapy.

CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans

These findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer and demonstrate that cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, it is shown that tumor regression required macrophages but not T cells or gemcitabine.

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

All human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination, showing that CD47 is a commonly expressed molecule on all cancers, its function to blockphagocytosis is known, and blockade of its function leads to tumor cell phagcytosis and elimination.

Macrophages eliminate circulating tumor cells after monoclonal antibody therapy.

It is found that antibody-dependent phagocytosis by macrophages is a prominent mechanism for removal of tumor cells from the circulation in a murine tumor cell opsonization model and may help to optimize mAb therapeutic strategies for patients with cancer by helping to enhance macrophage recruitment and activity.

The cellular and molecular origin of tumor-associated macrophages

In mice, mammary tumor growth induces the accumulation of tumor-associated macrophage that are phenotypically and functionally distinct from mammary tissue macrophages, which reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.

Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

It is demonstrated that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo, with a higher phagocytosis rate by M1 macrophage subtypes.

Intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations

Intravital microscopy in a model of breast cancer to provide unique insight into cellular composition and real-time dynamics of the stromal microenvironment is used and the effects of targeted therapy against CSF-1R, an important myeloid cell mitogen receptor, are characterized.