Dataset Information

Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.

ABSTRACT: PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer.

SUBMITTER: Van Allen EM

PROVIDER: S-EPMC4527885 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.

Van Allen Eliezer M EM Golay Hadrien G HG Liu Yan Y Koyama Shohei S Wong Karrie K Taylor-Weiner Amaro A Giannakis Marios M Harden Maegan M Rojas-Rudilla Vanesa V Chevalier Aaron A Thai Tran T Lydon Christine C Mach Stacy S Avila Ada G AG Wong Joshua A JA Rabin Alexandra R AR Helmkamp Joshua J Sholl Lynette L Carter Scott L SL Oxnard Geoffrey G Janne Pasi P Getz Gad G Lindeman Neal N Hammerman Peter S PS Garraway Levi A LA Hodi F Stephen FS Rodig Scott J SJ Dranoff Glenn G Wong Kwok-Kin KK Barbie David A DA

Cancer immunology research 20150526 8

PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that pr ...[more]

PMID: 26014096

Dataset Information

Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.

Publications

Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade.
| S-EPMC8286544 | biostudies-literature

Deep learning to estimate durable clinical benefit and prognosis from patients with non-small cell lung cancer treated with PD-1/PD-L1 blockade.
| S-EPMC9677530 | biostudies-literature

Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity.
| S-EPMC5023369 | biostudies-literature

The Tumor Microenvironment Regulates Sensitivity of Murine Lung Tumors to PD-1/PD-L1 Antibody Blockade.
| S-EPMC5787226 | biostudies-literature

Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer.
| S-EPMC8222224 | biostudies-literature

PD-L1 in Systemic Immunity: Unraveling Its Contribution to PD-1/PD-L1 Blockade Immunotherapy.
| S-EPMC7460585 | biostudies-literature

Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer.
| S-EPMC6209395 | biostudies-literature

PD-1/PD-L1 blockade in renal cell cancer.
| S-EPMC5555220 | biostudies-literature

RANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer.
| S-EPMC5980384 | biostudies-literature

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade.
| S-EPMC8268315 | biostudies-literature