First-Line Treatment of Non-Small-Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors

Bylicki, Olivier; Barazzutti, H.; Paleiron, Nicolas; Margery, J.; Assié, Jean-Baptiste; Chouaïd, C.

doi:10.1007/s40259-019-00339-4

Cited by 41 publications

(32 citation statements)

References 61 publications

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“…However, drug resistance limits the therapeutic benefits of a single PD-L1 inhibitor [12][13][14]. As such, a combination of PD-L1 inhibitors and other treatments has been proposed to reduce drug resistance rate hence improving the clinical response rate [15][16][17][18][19][20]. For instance, PD-L1 inhibitors combined with immune factors have a stronger anticarcinoma effect than PD-L1 inhibitors used alone [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Relationship between IL10 and PD-L1 in Liver Hepatocellular Carcinoma Tissue and Cell Lines

Qian

Chen

et al. 2020

BioMed Research International

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Background. Despite the large-scale clinical application of programmed death-ligand 1 (PD-L1) monoclonal antibody, reduction in its clinical response rate has become a gradual problem. As such, use of PD-L1 monoclonal antibody in combination with other anticarcinoma drugs has been the main strategy in improving its efficacy. Interleukin 10 (IL10) is a recognized inflammatory and immunosuppressive factor. Previous studies have suggested that there is a link between PD-L1 and IL10. Objective. This study was aimed at clarifying the relationship between PD-L1 and IL10 in liver hepatocellular carcinoma (LIHC) and whether IL10 enhances the efficacy of PD-L1 inhibitor. Methods. Expression levels of PD-L1 and IL10 in carcinoma and adjacent tissues were tested by immunochemistry, Western blotting, and RT-PCR. Survival duration and follow-up data of each patient were recorded. LIHC cell lines Bel7405 and MHCC 97-H were used for in vitro experiments. Exogenous IL10 and anti-IL10 were added to cell supernatant. Expression level of PD-L1 in the LIHC cell lines was determined using Western blotting and ELISA. CCK8 and transwell assays were adopted to examine the effect of PD-L1 combined with IL10 on proliferation, invasion, and metastasis of LIHC cells. Results. The survival period of patients with low expression of IL10 was longer than that of patients with high expression (P=0.01). Overexpression of PD-L1 increased the IL10 and Met levels in LIHC tissues and cell lines. IL10 downregulated the expression level of PD-L1 and enhanced the efficacy of crizotinib via the Met signaling pathway in the LIHC cells. Conclusions. A combination of IL10 and PD-L1 inhibitor holds great promise as an effective treatment for LIHC.

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Section: Introductionmentioning

confidence: 99%

Relationship between IL10 and PD-L1 in Liver Hepatocellular Carcinoma Tissue and Cell Lines

Qian

Chen

et al. 2020

BioMed Research International

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“…Among them, pembrolizumab is the only immune checkpoint inhibitor approved by the FDA and the National Medical Products Administration (NMPA) in China for first-line treatment of NSCLC. 11…”

Section: Introductionmentioning

confidence: 99%

<p>A Review About Pembrolizumab in First-Line Treatment of Advanced NSCLC: Focus on KEYNOTE Studies</p>

Qu¹,

Wang²,

Jiang³

et al. 2020

CMAR

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Lung cancer is currently the malignant tumor with the highest incidence and mortality in the world, while non-small cell lung cancer (NSCLC) is the most common pathological type of lung caner. In the past few decades, the only treatment options available for advanced NSCLC patients have been targeted therapy or chemotherapy, but these therapies are inevitably tolerated by tumors. The discovery of immune checkpints that mediate the immune escape of tumor cells have been promoting a series of immune checkpoint inhibitors to be used in cancer treatment and achieved great results. Among them, pembrolizumab is currently the only PD-1 inhibitor approved for first-line treatment of NSCLC, whether it is monotherapy or combination therapy, for creditable performance in KEYNOTE studies. In this review, we systematically integrate the latest series of clinical trial results, pharmacological mechanisms, adverse events (AEs) and predictive biomarkers in the first-line treatment of NSCLC. We hope pembrolizumab could become a better choice for more clinicians and benefit more patients with advanced NSCLC.

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“…[23][24][25][26] In particular, the development of immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies could lead to a major paradigm shift in standard therapy for patients with advanced NSCLC. 27 In addition, recently, it has been reported that immunotherapy targeting the neoantigen, which is a cancer-specific antigen derived from mutated amino acid sequences, has a remarkable anti-tumor effect against various carcinomas. 28,29 Neoantigens often have the advantage of being highly immunogenic and having a high affinity for T-cell receptors (TCR) on cancer-specific CTL.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of immunotherapy targeting the neoantigen derived from epidermal growth factor receptor T790M/C797S mutation in non–small cell lung cancer

et al. 2020

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Lung cancer is the leading cause of cancer‐related deaths worldwide. Epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKI) often have good clinical activity against non–small cell lung cancer (NSCLC) with activating EGFR mutations. Osimertinib, which is a third‐generation EGFR‐TKI, has a clinical effect even on NSCLC harboring the threonine to methionine change at codon 790 of EGFR (EGFR T790M) mutation that causes TKI resistance. However, most NSCLC patients develop acquired resistance to osimertinib within approximately 1 year, and 40% of these patients have the EGFR T790M and cysteine to serine change at codon 797 (C797S) mutations. Therefore, there is an urgent need for the development of novel treatment strategies for NSCLC patients with the EGFR T790M/C797S mutation. In this study, we identified the EGFR T790M/C797S mutation‐derived peptide (790‐799) (MQLMPFGSLL) that binds the human leukocyte antigen (HLA)‐A*02:01, and successfully established EGFR T790M/C797S‐peptide‐specific CTL clones from human PBMC of HLA‐A2 healthy donors. One established CTL clone demonstrated adequate cytotoxicity against T2 cells pulsed with the EGFR T790M/C797S peptide. This CTL clone also had high reactivity against cancer cells that expressed an endogenous EGFR T790M/C797S peptide using an interferon‐γ (IFN‐γ) enzyme‐linked immunospot (ELISPOT) assay. In addition, we demonstrated using a mouse model that EGFR T790M/C797S peptide‐specific CTL were induced by EGFR T790M/C797S peptide vaccine in vivo. These findings suggest that an immunotherapy targeting a neoantigen derived from EGFR T790M/C797S mutation could be a useful novel therapeutic strategy for NSCLC patients with EGFR‐TKI resistance, especially those resistant to osimertinib.

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First-Line Treatment of Non-Small-Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors

Cited by 41 publications

References 61 publications

Relationship between IL10 and PD-L1 in Liver Hepatocellular Carcinoma Tissue and Cell Lines

Relationship between IL10 and PD-L1 in Liver Hepatocellular Carcinoma Tissue and Cell Lines

<p>A Review About Pembrolizumab in First-Line Treatment of Advanced NSCLC: Focus on KEYNOTE Studies</p>

Efficacy of immunotherapy targeting the neoantigen derived from epidermal growth factor receptor T790M/C797S mutation in non–small cell lung cancer

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