PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade

Srour, Nivine; Villarreal, Oscar D.; Hardikar, Swanand; Yu, Zhenbao; Preston, Samuel E.J.; Miller, Wilson H.; Szewczyk, Magdelena M; Baršytė-Lovejoy, Dalia; Chen, Taiping; Rincón, Sonia V. del; Richard, Stéphane

doi:10.1016/j.celrep.2022.110582

Cited by 38 publications

(22 citation statements)

References 108 publications

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“…Various studies have indicated that cells expressing low MITF are intrinsically resistant to MAPK pathway inhibitors (such as BRAFi/ MEKi) and immunotherapies (anti-PD-1 and anti-CTLA-4 antibodies), often persist, and have the highest ability to form tumors and metastasize [ 8 , 9 , 67 , [69] , [70] , [71] , [72] ]. Importantly, dedifferentiated melanomas characterized by low MITF and low MDAs are resistant to immunotherapy as well [ 15 , 16 , 73 , 74 ]. Consistently, differentiated dark stained tumors are also infiltrated with higher density of immune cells (immunologically hot) [69] .…”

Section: Discussionmentioning

confidence: 99%

S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas

et al. 2023

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Section: Discussionmentioning

confidence: 99%

S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas

et al. 2023

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“…Importantly, such agents may in uence expression of non-IFN pathway genes in cancer cells as well, and they may also act on other cell populations within the TME in both IFN-dependent and non-IFN-dependent ways. Regardless, such strategies have been shown to potentiate anti-tumor immune responses when combined with ICB therapy, and in some cases these synergistic effects have been directly related to increased IFN pathway activity in cancer cells themselves [41][42][43][44].…”

Section: Tumor-intrinsic Defects In Type I and Type Ii Interferon Sig...mentioning

confidence: 99%

Genetic dysregulation of immunologic and oncogenic signaling pathways associated with tumor-intrinsic immune resistance: a molecular basis for combination targeted therapy-immunotherapy for cancer

Hargadon

2023

Cell. Mol. Life Sci.

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Since the turn of the century, advances in targeted therapy and immunotherapy have revolutionized the treatment of cancer. Although these approaches have far outperformed traditional therapies in various clinical settings, both remain plagued by mechanisms of innate and acquired resistance that limit therapeutic e cacy in many patients. With a focus on tumor-intrinsic resistance to immunotherapy, this review highlights our current understanding of the immunologic and oncogenic pathways whose genetic dysregulation in cancer cells enables immune escape. Emphasis is placed on genomic, epigenomic, transcriptomic, and proteomic aberrations that in uence the activity of these pathways in the context of immune resistance. Speci cally, the role of pathways that govern interferon signaling, antigen processing and presentation, and immunologic cell death as determinants of tumor immune susceptibility are discussed. Likewise, mechanisms of tumor immune resistance mediated by dysregulated RAS-MAPK, WNT, PI3K-AKT-mTOR, and cell cycle pathways are described. Finally, this review brings attention to the ways in which genetic dysregulation of these immunologic and oncogenic signaling pathways are informing the design of targeted interventions to restore immune susceptibility of cancer cells and enhance immunotherapeutic e cacy through combination targeted therapy-immunotherapy regimens that overcome the resistance mechanisms known to limit the success of monotherapies.

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“…Recently, PRMT7 was identified as a new target to sensitize melanoma cells to cancer immunotherapy. 116 It was shown that combining anti-PD-1 and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy with PRMT7 deletion or PRMT7 inhibition using SGC3027, a cell permeable prodrug, 117 enhances anti-tumor responsiveness to the immune checkpoint blockade in a melanoma mouse model. 116 PRMT7-deficient B16.F10 melanoma cells exhibit increased dsRNA repetitive element expression, mimicking viral induction of the RIG-I pathway ( Figure 4D ).…”

Section: Prmts In Cancer Immunotherapymentioning

confidence: 99%

The Influence of Arginine Methylation in Immunity and Inflammation

Srour¹,

Khan²,

Richard³

2022

JIR

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Exploration in the field of epigenetics has revealed that protein arginine methyltransferases (PRMTs) contribute to disease, and this has given way to the development of specific small molecule compounds that inhibit arginine methylation. Protein arginine methylation is known to regulate fundamental cellular processes, such as transcription; pre-mRNA splicing and other RNA processing mechanisms; signal transduction, including the anti-viral response; and cellular metabolism. PRMTs are also implicated in the regulation of physiological processes, including embryonic development, myogenesis, and the immune system. Finally, the dysregulation of PRMTs is apparent in cancer, neurodegeneration, muscular disorders, and during inflammation. Herein, we review the functions of PRMTs in immunity and inflammation. We also discuss recent progress with PRMTs regarding the modulation of gene expression related to T and B lymphocyte differentiation, germinal center dynamics, and anti-viral signaling responses, as well as the clinical relevance of using PRMT inhibitors alone or in combination with other drugs to treat cancer, immune, and inflammatory-related diseases.

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PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade

Cited by 38 publications

References 108 publications

S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas

S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas

Genetic dysregulation of immunologic and oncogenic signaling pathways associated with tumor-intrinsic immune resistance: a molecular basis for combination targeted therapy-immunotherapy for cancer

The Influence of Arginine Methylation in Immunity and Inflammation

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