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CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer.

Cancer Cell. 2020; 
Zhang H, Christensen CL, Dries R, Oser MG, Deng J, Diskin B, Li F, Pan Y, Zhang X, Yin Y, Papadopoulos E, Pyon V, Thakurdin C, Kwiatkowski N, Jani K, Rabin AR, Castro DM, Chen T, Silver H, Huang Q, Bulatovic M, Dowling CM, Sundberg B, Leggett A, Ranieri M, Han H, Li S, Yang A, Labbe KE, Almonte C, Sviderskiy VO, Quinn M, Donaghue J, Wang ES, Zhang T, He Z, Velcheti V, Hammerman PS, Freeman GJ0, Bonneau R, Kaelin WG Jr, Sutherland KD, Kersbergen A, Aguirre AJ, Yuan GC, Rothenberg E, Miller G, Gray NS, Wong KK.
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Catalog Peptides Subsequently, DMSO-conditioned medium or YKL-5-124-conditioned medium were collected and added to above single- cell suspension in a 96-well U-bottom plate in the presence of Ova257–264 peptide (10 mg/ml, GenScript, Cat#RP10611) for 4 days as previously described Get A Quote

摘要

Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling. These tumor-intrinsic events provoke a robust immune surveillance program elicited by T cells, which is further enhanced by the addition of immune-checkpoint blockade. Combining YKL-5-124 with anti-PD-1 offers significant survival benefit in multiple highly... More

关键词

CDK7; YKL-5-124; anti-tumor immunity; cell cycle; genome instability; immune checkpoint blockade; immunotherapy; replication stress; single-cell analysis; small cell lung cancer