PLX3397 inhibits the accumulation of intra‐tumoral macrophages and improves bromodomain and extra‐terminal inhibitor efficacy in melanoma

Erkes, Dan A.; Rosenbaum, Sheera; Field, Conroy O.; Chervoneva, Inna; Villanueva, Jessie; Aplin, Andrew E.

doi:10.1111/pcmr.12845

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…The small molecule drug PLX3397 targets CSF1R signaling and reprograms intra-tumoral immune suppressive myeloid cells ( 92 ), and has been shown to convert immune suppressive M-DSCs to a more proinflammatory tumoricidal phenotype ( 93 , 94 ). PLX3397was approved by the FDA in 2019 for use in the treatment of diffuse type tenosynovial giant cell tumors (dt-TGCT), a rare and often unresectable non-life-threatening cancer of the tendon sheath that is driven by CSF-1 expressing TAMs ( 95 ).…”

Section: Therapeutic Targeting Of Immune Suppressive Macrophages and ...mentioning

confidence: 99%

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

2023

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Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers current strategies targeting myeloid suppressor cells in the TME to enhance anti-tumoral immunity, including strategies that target chemokine receptors to deplete selected immune suppressive myeloid cells and relieve the inhibition imposed on the effector arms of adaptive immunity. Remodeling the TME can in turn improve the activity of other immunotherapies such as checkpoint blockade and adoptive T cell therapies in immunologically “cold” tumors. When possible, in this review, we have provided evidence and outcomes from recent or current clinical trials evaluating the effectiveness of the specific strategies used to target myeloid cells in the TME. The review seeks to provide a broad overview of how myeloid cell targeting can become a key foundational approach to an overall strategy for improving tumor responses to immunotherapy.

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Section: Therapeutic Targeting Of Immune Suppressive Macrophages and ...mentioning

confidence: 99%

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

2023

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“…Monoclonal antibody (RG7155) reduced the number of F4/80+ TAMs and increased the ratio of CD8+/CD4+ T cells by inhibiting CSF-1R [45] . In melanoma, small molecule PLX3397 (CSF-1R inhibitor) inhibits the accumulation of TAMs, and in combination with extra-terminal inhibitors can enhance the efficacy of tumor therapy [46] . In recent years, studies have found that traditional Chinese medicine can also improve the immune function of patients by regulating TAMs, thus achieving the anti-tumor effect.…”

Section: Targeting Macrophage Recruitmentmentioning

confidence: 99%

Tumor-Associated Macrophages as Treatment Target in Colorectal Cancer

2022

FMSR

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Colorectal cancer (CRC) is one of the common malignant tumors in the digestive tract, and its treatment and prognosis are affected by many factors. Macrophages are cells that participate in innate immunity. Macrophages are cells that participate in innate immunity, maintain the body and resist the invasion of foreign pathogens, and play a supporting role in different organs and tissues. In the tumor microenvironment (TME), macrophages are called tumor-associated macrophages (TAMs), and they play an important role in tumor cell proliferation, metastasis, angiogenesis, and immunosuppression. In this article, we reviewed the interaction between TAMs and tumor cells, discussed the origin and polarization of TAMs, and described the role of TAMs in tumorigenesis and development, invasion and metastasis, and immunosuppression. Finally, we briefly summarized tumor treatment options targeting TAMs to provide new ideas for subsequent tumor research and treatment.

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“…PLX51107, a next-generation BETi, impaired tumor growth to differing degrees in BRAF V600E syngeneic mouse models, effects that were linked to the influx of TAMs. Tumors that were poorly responsive to BET inhibition displayed an increased influx of pro-tumoral macrophages and the addition of PLX3397 resulted in improved response rates to PLX51107, offering a novel combination therapy for metastatic CM patients [ 234 ]. In another study, PLX51107 slowed the growth of mouse BRAF V600E melanoma tumors by inducing the CD8 + T cell-mediated anti-tumor effects; moreover, PLX51107 proved to be an effective second-line therapy for CM tumors that harbored resistance to PD1/PDL1 checkpoint inhibition [ 264 ].…”

Section: Epigenetics-based Therapies For CMmentioning

confidence: 99%

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

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PLX3397 inhibits the accumulation of intra‐tumoral macrophages and improves bromodomain and extra‐terminal inhibitor efficacy in melanoma

Cited by 9 publications

References 40 publications

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

Tumor-Associated Macrophages as Treatment Target in Colorectal Cancer

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

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