Expression of PD-1 and Its Ligands, PD-L1 and PD-L2, in Smokers and Never Smokers with KRAS-Mutant Lung Cancer

Calles, Antonio; Liao, Xiaoyun; Sholl, Lynette M.; Rodig, Scott J.; Freeman, Gordon J.; Butaney, Mohit; Lydon, Christine; Dahlberg, Suzanne E.; Hodi, F. Stephen; Oxnard, Geoffrey R.; Jackman, David M.; Jänne, Pasi A.

doi:10.1097/jto.0000000000000687

Cited by 208 publications

(178 citation statements)

References 42 publications

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“…In addition, smoking status may relate with well-known predictive markers such as PD-L1 expression. Calles et al 25 found that higher PD-L1 expression intensity was more frequent in smokers, which is associated with increased pack years in MPDL3280A treatment. Cha et al 54 also confirmed that in lung adenocarcinoma, higher PD-L1 expression was more prevalent among former or current smokers (p = 0.026), which was associated with more pack years (p = 0.016).…”

Section: Smoking Statusmentioning

confidence: 99%

“…24 Human tumors have also been documented to express PD-L2, whereas its roles in tumorigenesis may share some differences with PD-L1 that are not very coherent. 25,26 Clinical studies on NSCLC show that the promising response rate (RR) is negatively correlated with PD-L1 expression on tumor-infiltrating immune cells (TILs) or tumor cells. Furthermore, anti-PD-1/PD-L1 therapy may not be confined to NSCLC cell types, given that no difference in the pooled objective response rates (ORRs) was observed between nonsquamous and squamous cell lung cancers in a meta-analysis.…”

Section: Pd-1/pd-l1-blocking Inhibitors and Clinical Relevancementioning

confidence: 99%

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Highlights on immune checkpoint inhibitors in non–small cell lung cancer

Shen

Ren²

2017

Tumour Biol.

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The treatment of advanced or refractory non-small cell lung cancer has been historically difficult owing to the lack of studies on effective systemic cure. The progress in lung cancer treatment has plateaued, necessitating new options for additional benefits. Immune checkpoint proteins are co-inhibitory factors that can diminish the antigen-specific immune responses by attenuating the regulatory role of cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1, lymphocyte-activation gene 3, and T-cell immunoglobulin mucin-3. The therapeutic strategies targeting immune checkpoints mainly focus on the monoclonal antibody of these regulatory factors, which may facilitate clinical decision making. An enhanced understanding of the drug-resistance mechanisms and the therapeutic efficacy regulation will provide opportunities to improve the clinical outcomes of non-small cell lung cancer patients. Preclinical and clinical trials on these key immune-regulatory agents, which has heralded a new era in immuno-oncology in non-small cell lung cancer treatment, are currently in development. KeywordsNon-small cell lung cancer, immune checkpoint, cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1, programmed cell death ligand-1, tumor immunotherapy Date

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Section: Smoking Statusmentioning

confidence: 99%

Section: Pd-1/pd-l1-blocking Inhibitors and Clinical Relevancementioning

confidence: 99%

Highlights on immune checkpoint inhibitors in non–small cell lung cancer

Shen

Ren²

2017

Tumour Biol.

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“…133,136 Targeted therapy is not currently available for patients with KRAS mutations, although immune checkpoint inhibitors appear to be effective; MEK inhibitors are in clinical trials. 97,127,137,138 Targeted Therapies Specific targeted therapies are available for the treatment of advanced NSCLC. [139][140][141] Erlotinib, gefitinib, and afatinib are small molecule inhibitors of EGFR; osimertinib targets T790M.…”

Section: Kras Mutationsmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

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“…The complexity of KRAS mutations has been further magnified by the specific mutation and the presence of co-mutations. For instance, patients with KRAS and LKB1 co-mutation have a poor overall prognosis and are insensitive to immune checkpoint inhibition (40). A class of direct KRAS inhibitors have recently entered clinical investigations.…”

Section: Other Treatable Driver Mutationsmentioning

confidence: 99%