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1 May 2019
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Sen and colleagues showed that treatment of human small cell lung cancer (SCLC) cell lines with inhibitors of the DNA damage response (DDR) components CHK1 and PARP resulted in increased expression of PD-L1 Further, inhibition of either CHK1 or PARP in immunocompetent genetically engineered mouse models (GEMM) of SCLC resulted in increased levels of cytosolic DNA, which activates the cGAS–STING innate immune signaling pathway to induce IRF3 activation and subsequently drive IFNβ-mediated increases in PD-L1 expression and T-cell recruitment in SCLC GEMMs Consistent with these findings, treatment with a CHK1 or PARP inhibitor enhanced the efficacy of anti–PD-L1 therapy and resulted in SCLC tumor regression in vivo Together, these findings suggest that combined targeting of DDR proteins and immune checkpoint blockade is a potential therapeutic strategy for patients with SCLC For details, please see the article by Sen and colleagues on page 646. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
In This Issue
In the Spotlight
Review
Research Briefs
Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel AKT1 Fusion–Driven Cancer
Emily K. Slotkin; Daniel Diolaiti; Neerav N. Shukla; Filemon S. Dela Cruz; Jennifer J. Clark; Gunes Gundem; Venkata D. Yellapantula; Max F. Levine; Daoqi You; Peilin Ma; Sagarika Pachhal; Glorymar Ibanez Sanchez; Ryma Benayed; Achim A. Jungbluth; Lillian M. Smyth; Audrey Mauguen; Irena Gushterova; Hongxu Ding; Lee Spraggon; Robert Darnell; Andrea Califano; Marc Ladanyi; Elli Papaemmanuil; Andrew L. Kung; David M. Hyman; Stephen S. Roberts
Author Choice
A Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression
Francesca R. Auciello; Vinay Bulusu; Chet Oon; Jacqueline Tait-Mulder; Mark Berry; Sohinee Bhattacharyya; Sergey Tumanov; Brittany L. Allen-Petersen; Jason Link; Nicholas D. Kendsersky; Esmee Vringer; Michelle Schug; David Novo; Rosa F. Hwang; Ronald M. Evans; Colin Nixon; Craig Dorrell; Jennifer P. Morton; Jim C. Norman; Rosalie C. Sears; Jurre J. Kamphorst; Mara H. Sherman
Research Articles
Author Choice
Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases
Grant M. Fischer; Ali Jalali; David A. Kircher; Won-Chul Lee; Jennifer L. McQuade; Lauren E. Haydu; Aron Y. Joon; Alexandre Reuben; Mariana P. de Macedo; Fernando C. L. Carapeto; Chendong Yang; Anuj Srivastava; Chandrashekar R. Ambati; Arun Sreekumar; Courtney W. Hudgens; Barbara Knighton; Wanleng Deng; Sherise D. Ferguson; Hussein A. Tawbi; Isabella C. Glitza; Jeffrey E. Gershenwald; Y. N. Vashisht Gopal; Patrick Hwu; Jason T. Huse; Jennifer A. Wargo; P. Andrew Futreal; Nagireddy Putluri; Alexander J. Lazar; Ralph J. DeBerardinis; Joseph R. Marszalek; Jianjun Zhang; Sheri L. Holmen; Michael T. Tetzlaff; Michael A. Davies
Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer
Triparna Sen; B. Leticia Rodriguez; Limo Chen; Carminia M. Della Corte; Naoto Morikawa; Junya Fujimoto; Sandra Cristea; Thuyen Nguyen; Lixia Diao; Lerong Li; Youhong Fan; Yongbin Yang; Jing Wang; Bonnie S. Glisson; Ignacio I. Wistuba; Julien Sage; John V. Heymach; Don L. Gibbons; Lauren A. Byers
BCL6 Evolved to Enable Stress Tolerance in Vertebrates and Is Broadly Required by Cancer Cells to Adapt to Stress
Tharu M. Fernando; Rossella Marullo; Benet Pera Gresely; Jude M. Phillip; Shao Ning Yang; Geoffrey Lundell-Smith; Ingrid Torregroza; Haelee Ahn; Todd Evans; Balázs Győrffy; Gilbert G. Privé; Masayuki Hirano; Ari M. Melnick; Leandro Cerchietti
News in Brief
News in Depth
Research Watch
Clinical Trials
Epigenetics
Genome Stability
Immunotherapy
Melanoma
Metabolism
Metastasis
Mutations
Oncogenes
Prostate Cancer
Stem Cells
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NOTICE: This notice serves to inform the reader that, in 2023, AACR received a donation by Pfizer of the rights to royalties from the sale within the United States of Bavencio® (avelumab), a pharmaceutical owned by Merck. If any resulting funds are received, they would not be used to directly support any specific publication or author. If an individual article is published that deals with this particular drug, such article will include standard financial disclosures per AACR journal policy. For more detail regarding AACR’s established policies for authors, please go to https://aacrjournals.org/pages/editorial-policies#coi.