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

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

Cell reports (2022-03-31)
Nivine Srour, Oscar D Villarreal, Swanand Hardikar, Zhenbao Yu, Samuel Preston, Wilson H Miller, Magdelena M Szewczyk, Dalia Barsyte-Lovejoy, Han Xu, Taiping Chen, Sonia V Del Rincón, Stéphane Richard
ABSTRACT

Despite the success of immune checkpoint inhibitor (ICI) therapy for cancer, resistance and relapse are frequent. Combination therapies are expected to enhance response rates and overcome this resistance. Herein, we report that combining PRMT7 inhibition with ICI therapy induces a strong anti-tumor T cell immunity and restrains tumor growth in vivo by increasing immune cell infiltration. PRMT7-deficient B16.F10 melanoma exhibits increased expression of genes in the interferon pathway, antigen presentation, and chemokine signaling. PRMT7 deficiency or inhibition with SGC3027 in B16.F10 melanoma results in reduced DNMT expression, loss of DNA methylation in the regulatory regions of endogenous retroviral elements (ERVs) causing their increased expression. PRMT7-deficient cells increase RIG-I and MDA5 expression with a reduction in the H4R3me2s repressive histone mark at their gene promoters. Our findings identify PRMT7 as a regulatory checkpoint for RIG-I, MDA5, and their ERV-double-stranded RNA (dsRNA) ligands, facilitating immune escape and anti-tumor T cell immunity to restrain tumor growth.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Actinomycin D, from Streptomyces sp., suitable for cell culture, ≥95%
Pricing and availability is not currently available.
Sigma-Aldrich
GenElute Mammalian Total RNA Miniprep Kit, sufficient for 70 purifications
Pricing and availability is not currently available.
Sigma-Aldrich
Anti-PRMT7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Pricing and availability is not currently available.