Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

Stafford, Jason H.; Hirai, Takahisa; Deng, Lei; Chernikova, Sophia B.; Urata, Kimiko; West, Brian L.; Brown, J. Martin

doi:10.1093/neuonc/nov272

Cited by 176 publications

(165 citation statements)

References 47 publications

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“…Both act as tumor suppressors by promoting TAMs with an antitumor phenotype [71][72][73][74][75] or by decreasing monocyte recruitment. [76][77][78][79][80] This beneficial effect is partially compromised by activation of HIF-1α pathways that lead to an angiogenic counterresponse. 81 In pancreatic adenocarcinoma and murine breast cancers, activation of the Akt/phosphatidylinositol-3 kinase pathway by prolonged exposure to sorafenib triggers TAMs to adapt a tumor supportive and pro-angiogenic phenotype.…”

Section: Tams and Anti-angiogenic Therapymentioning

confidence: 99%

The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

et al. 2017

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"Tumor-associated macrophages" (TAMs) form a significant cell population in malignant tumors and contribute to tumor growth, metastasis, and neovascularization. Gliomas are characterized by extensive neo-angiogenesis, and knowledge of the role of TAMs in neovascularization is important for future anti-angiogenic therapies. The phenotypes and functions of TAMs are heterogeneous and more complex than a classification into M1 and M2 inflammation response types would suggest. In this review, we provide an update on the current knowledge of the ontogeny of TAMs, focusing on diffuse gliomas. The role of TAMs in the regulation of the different processes in tumor angiogenesis is highlighted and the most recently discovered mechanisms by which TAMs mediate resistance against current antivascular therapies are mentioned. Novel compounds tested in clinical trials are discussed and brought in relation to different TAM-related angiogenesis pathways. In addition, potential therapeutic targets used to intervene in TAM-regulated tumor angiogenesis are summarized.

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Section: Tams and Anti-angiogenic Therapymentioning

confidence: 99%

The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

et al. 2017

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“…Moreover, irradiated cancer cells have been shown to drive undifferentiated macrophages towards M2 polarization 27,30–32 despite the adjuvant content of irradiated cells. These macrophages limit the efficacy of radiation therapy in a range of mouse models 33–37 , and preventing M2 polarization enhances radiation tumor control by radiation therapy 27,38 . Taken together, these data suggest that the endogenous adjuvant activity of irradiated cancer cells is often insufficient to overcome the preexisting suppressive environment of the tumor and may even enhance the suppressive M2 macrophage environment.…”

Section: Introductionmentioning

confidence: 99%

Stimulating Innate Immunity to Enhance Radiation Therapy–Induced Tumor Control

Baird

Monjazeb

Shah

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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Novel ligands that target Toll-like receptors and other innate recognition pathways represent a potent strategy for modulating innate immunity to generate anti-tumor immunity. While many of the current clinically successful immunotherapies target adaptive T-cell responses, both pre-clinical and clinical studies suggest that adjuvants have the potential to enhance the scope and efficacy of cancer immunotherapy. Radiation may be a particularly good partner to combine with innate immune therapies, since it is a highly efficient means to kill cancer cells, but may fail to send the appropriate inflammatory signals needed to act as an efficient endogenous vaccine. This may explain why although radiation therapy is a highly used cancer treatment, true abscopal effects – regression of disease outside the field without additional systemic therapy – are extremely rare. This review focuses on efforts to combine innate immune stimuli as adjuvants with radiation, creating a distinct and complementary approach from T cell targeted therapies to enhance anti-tumor immunity.

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“…Given the accumulation of myeloid cells in GBM tumor tissue, we hypothesized that myeloid recruitment factors secreted by tumor cells 40–43 would be elevated in patient serum. We assayed serum from 14 healthy donors, 17 Dex-treated GBM patients, and 8 steroid naïve GBM patients using the BioRad Bioplex human chemokine array, which quantifies 40 soluble analytes.…”

Section: Resultsmentioning

confidence: 99%

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

et al. 2018

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Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment factors that are associated with high-grade disease, both within the tumor and in circulation, is critical to identifying novel targets for immunotherapy. Furthermore, a better understanding of how therapeutic regimens, such as Dexamethasone (Dex), chemotherapy, and radiation, impact these factors will facilitate the design of therapies that can be targeted to the appropriate populations and retain efficacy when administered in combination with standard of care regimens. Here we perform quantitative analysis of tissue microarrays made of samples taken from grades I-III astrocytoma and glioblastoma (GBM, grade IV astrocytoma) to evaluate infiltration of myeloid markers CD163, CD68, CD33, and S100A9. Serum, flow cytometric, and Nanostring analysis allowed us to further elucidate the impact of Dex treatment on systemic biomarkers, circulating cells, and functional markers within tumor tissue. We found that common myeloid markers were elevated in Dex-treated grade I astrocytoma and GBM compared to non-neoplastic brain tissue and grade II-III astrocytomas. Cell frequencies in these samples differed significantly from those in Dex-naïve patients in a pattern that depended on tumor grade. In contrast, observed changes in serum chemokines or circulating monocytes were independent of disease state and were due to Dex treatment alone. Furthermore, these changes seen in blood were often not reflected within the tumor tissue.Conclusions: Our findings highlight the importance of considering perioperative treatment as well as disease grade when assessing novel therapeutic targets or biomarkers of disease.

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Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

Abstract: CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy.

Cited by 176 publications

References 47 publications

The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

Stimulating Innate Immunity to Enhance Radiation Therapy–Induced Tumor Control

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

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