PD-L1 copy number gains: a predictive biomarker for PD-1/PD-L1 blockade therapy?

Inoue, Yusuke; Osman, Murat; Suda, Takafumi; Sugimura, Haruhiko

doi:10.21037/tcr.2016.07.47

Cited by 4 publications

(2 citation statements)

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“…The use of antibodies against PD-1 has shown a favorable outcome in cancers with a high expression of PD-L1 ( 4 ). However, only a minority of PD-L1–positive patients with NSCLC respond to anti–PD-1 therapy due, in part, to intratumoral and temporal heterogeneity of pathologically regulated PD-L1 expression, underscoring the role of the pathophysiological state of the tumor microenvironment in dictating treatment response to anti–PD-1 therapy ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma

et al. 2020

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About 40% of patients with non–small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure. New immunotherapeutic modalities such as anti–PD-1 immune checkpoint blockade have shown promise; however, response to such strategies is highly variable across patients. Here, we show that our unique poly(2-oxazoline)–based nanomicellar formulation (PM) of Resiquimod, an imidazoquinoline Toll-like receptor (TLR) 7/8 agonist, had a superior tumor inhibitory effect in a metastatic model of lung adenocarcinoma, relative to anti–PD-1 therapy or platinum-based chemotherapy. Investigation of the in vivo immune status following Resiquimod PM treatment showed that Resiquimod-based stimulation of antigen-presenting cells in the tumor microenvironment resulted in the mobilization of an antitumor CD8+ immune response. Our study demonstrates the promise of poly(2-oxazoline)-formulated Resiquimod for treating metastatic NSCLC.

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Section: Introductionmentioning

confidence: 99%

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma

et al. 2020

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“…The use of antibodies against PD1 has shown a favorable outcome in cancers with a high expression of PDL1 (4). However, only a minority of PDL1 positive NSCLC patients respond to anti-PD1 therapy due in part to intratumoral and temporal heterogeneity of pathologically regulated PDL1 expression, underscoring the role of the pathophysiological state of the tumor microenvironment in dictating the treatment response to anti-PD1 treatment (5,6).…”

Section: Introductionmentioning

confidence: 99%

High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma

Vinod

Hwang

Azam

et al. 2019

Preprint

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About 40% of the NSCLC patients have Stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure. New immunotherapeutic modalities such as anti-PD1 checkpoint blockade have shown promise; however, response to such strategies is highly variable across patients. Here, we show that our novel poly(2-oxazoline) (POx) based nanomicellar formulation of Resiquimod, an imidazoquinoline TLR 7/8 agonist, had a superior tumor inhibitory effect in a metastatic model of lung adenocarcinoma, relative to anti-PD1 immune checkpoint blockade therapy as well as platinum-based chemotherapy, which is the mainstay of treatment for NSCLC. Investigation of the in vivo immune status following Resiquimod PM (POx micellar formulation of Resiquimod) treatment showed that Resiquimodbased stimulation of antigen-presenting cells in the tumor microenvironment resulted in the mobilization of anti-tumor CD8 + immune response. Our study demonstrates the promise of optimally delivered and nano-formulated Resiquimod as a new immunomodulating therapeutic strategy for the treatment of metastatic NSCLC.Due to the superior toxicity profile and synergistic effect of C 6 CP/AZD7762 and C 6 CP/VE-822 combinations, they were identified as lead candidates for in vivo study.

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Heterogeneity analysis of PD-L1 expression and copy number status in EBUS-TBNA biopsy specimens of non-small cell lung cancer: Comparative assessment of primary and metastatic sites

et al. 2019

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PD-L1 copy number gains: a predictive biomarker for PD-1/PD-L1 blockade therapy?

Cited by 4 publications

References 0 publications

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma

High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma

Heterogeneity analysis of PD-L1 expression and copy number status in EBUS-TBNA biopsy specimens of non-small cell lung cancer: Comparative assessment of primary and metastatic sites

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