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KIR Polymorphism is Associated with Primary Resistance to PD-1 Blockade in Lung Cancer

ABSTRACT: Adaptive immune escape of tumor cells by upregulation of ligands for programmed death 1 (PD-1) has been identified as an important and targetable pathway in many cancer types. Many clinical trials have demonstrated that targeting PD-1 or its ligand PD-L1 with immune checkpoint inhibitors (ICI) can restore anti-tumor immunity and induce durable remission. In patients with non-small cell lung cancer (NSCLC), several trials have demonstrated a survival benefit with ICI in patients with metastatic and locally advanced NSCLC.Yet, most patients have primary resistance to PD-1 or PD-L1 blockade during treatment: approximately 20% of unselected patients with NSCLC achieve a partial response while 40-50% have progressive disease as best response. Understanding mechanisms of primary resistance to PD-(L)1 blockade is important in the search for potentially targetable pathways and may ultimately allow discrimination between patients that benefit from PD-(L)1 blockade and those requiring combination or other approaches. We collected PBMCs and serum samples from 35 patients with NSCLC before and during PD-1 blockade treatment with nivolumab. We analyzed differentially expressed genes in CD8+ T cells from the peripheral blood of 5 patients with partial response and 5 patients with primary progressive disease to identify mechanisms of resistance to PD-1 therapy. Cells were collected from samples taken before and after 4 weeks of treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE111414 | GEO | 2021/03/01

REPOSITORIES: GEO

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Soluble immune-checkpoint factors as a complementary biomarker for PD-1 blockade reflect exhaustion of antitumor immunity

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Liu2023 - Predicting the efficacy of immune checkpoint inhibitors monotherapy in advanced non-small cell lung cancer: a machine learning method based on multidimensional data

Project description:Immunotherapy has improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC), but only a small subset of patients achieved clinical benefit. The purpose of our study was to integrate multidimensional data using a machine learning method to predict the therapeutic efficacy of immune checkpoint inhibitors (ICIs) monotherapy in patients with advanced NSCLC.The authors retrospectively enrolled 112 patients with stage IIIB-IV NSCLC receiving ICIs monotherapy. The random forest (RF) algorithm was used to establish efficacy prediction models based on five different input datasets, including precontrast computed tomography (CT) radiomic data, postcontrast CT radiomic data, combination of the two CT radiomic data, clinical data, and a combination of radiomic and clinical data. The 5-fold cross-validation was used to train and test the random forest classifier. The performance of the models was assessed according to the area under the curve (AUC) in the receiver operating characteristic (ROC) curve. Among these models(RF MLP LR XGBoost), our reproduced onnx models have better performance, especially for random forest. The response variable with a value (1/0) indicates the (efficacy/inefficacy) of PD-1/PD-L1 monotherapy in patients with advanced NSCLC

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Identification of clonal neoantigens derived from driver mutations in an EGFR mutated lung cancer patient benefitting from anti-PD-1

Project description:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been recommended as the first line therapy for non-small cell lung cancer (NSCLC) with EGFR mutations. However, acquired resistance to EGFR-TKIs is inevitable. Although anti- programmed cell death 1 (PD-1)/PD-ligand (PD-L1) immunotherapies have achieved great clinical success as second-line treatment for many cancer types, the clinical efficacy of anti-PD-1/PD-L1 blockades in EGFR mutated NSCLC patients has been demonstrated to be obviously lower than those without EGFR mutations. Here, we reported an advanced NSCLC patient with exon 19 deletion and T790M EGFR mutation benefitting from anti-PD-1 blockade therapy after acquiring resistance to EGFR-TKI. We characterized the mutational landscape of the patient with next-generation sequencing (NGS), and successfully identified neoantigen-specific T cell clones derived from EGFR exon 19 deletion, TP53 A116T and DENND6B R398Q mutations. Our findings support the potential application of immune checkpoint blockades in NSCLC patients with acquired resistance to EGFR-TKIs in the context of specific clonal neoantigens with high immunogenicity. Personalized immunomodulatory therapy targeting these neoantigens should be explored for better clinical outcomes in EGFR mutant NSCLC patients.

2020-06-30 | GSE150972 | GEO

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| phs001469 | dbGaP

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| EGAS00001005013 | EGA

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MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France3]

2021-12-08 | GSE190265 | GEO

MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [LLC1]

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2023-05-22 | GSE232730 | GEO

Gene-expression profiling on a HPV-related head and neck cancer patient with idiopathic CD4 lymphocytopenia and complete remission to checkpoint inhibitors

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2021-12-31 | GSE161785 | GEO

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