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
Project description:Immune checkpoint blockade (ICB) has demonstrated significant promise for the treatment of advanced malignancies. Anti-CTLA4 and ant-PD1 therapy can activate the immune system and result in durable control in diseases such as melanoma and non-small cell lung cancer.
Project description:We used in situ vaccination with autologous dendritic cell secreting CCL21, in combination with immune checkpoint inhibitor, anti-PD-1, to treat oncogene-driven non-small cell lung cancer in a murine model. The single cell transcriptome of the treated cancer tissues were measured.
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. These aberrations are indeed among the most frequent aberrations in lung SCC and correlate with SCC patient's poor prognosis. We precisely map regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC. We moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. Keywords: ArrayCGH, Lung Squamous Cell Carcinoma, 3q26.3, SOX2 Profiling of 26 advanced (stage III) lung SCC. Replicates : each tumor sample is hybridized together with a normal dna sample to one microarray. Each microarray contain 3 replicates per BAC clone.
Project description:The clinical benefit of immune checkpoint inhibitor (ICI) treatments in patients with advanced KRAS mutant non-small-cell lung cancer (NSCLC) is limited. Here, we found IBI351, a selective KRASG12C inhibitor, significantly enhanced the efficacy of anti-PD-1 antibody (αPD-1) in inhibiting tumor growth in vitro and in vivo. Mechanistically, IBI351 inhibited STAT3 activity, leading to downregulation of stanniocalcin 1 (STC1). STC1 anchors calreticulin (CRT) to the mitochondrial membrane; its downregulation promoted CRT translocation to the cancer cell surface, increasing the ‘eat me’ signal and enhancing T cell infiltration. In clinical specimens from KRASG12C mutant NSCLC patients treated with PD-1 inhibitors, low STC1 expression correlated with better treatment response and prolonged survival. Together, these findings demonstrate that IBI351 enhances ICI efficacy by suppressing the STAT3-STC1 axis and promoting CRT-mediated phagocytosis, supporting further clinical evaluation of this combination.
Project description:Small Cell Lung Cancer (SCLC) is the most aggressive type of lung cancer with early metastatic dissemination and invariable development of resistant disease for which no effective treatment is available to date. Mouse models of SCLC based on inactivation of Rb1 and Trp53 developed earlier showed frequent amplifications of two transcription factor genes: Nfib and Mycl. Overexpression of Nfib but not Mycl in SCLC mouse results in an enhanced and altered metastatic profile, and appears to be associated with genomic instability. NFIB promotes tumor heterogeneity with the concomitant expansive growth of poorly differentiated, highly proliferative, and invasive tumor cell populations. Consistent with the mouse data, NFIB expression in high-grade human neuroendocrine carcinomas correlates with advanced stage III/IV disease warranting its further assessment as a potentially valuable progression marker in a clinical setting. Genomic DNA from mouse small cell lung tumor samples was analyzed by mate pair sequencing and low coverage sequencing. And RNA from Nfib overexpressing mouse small cell lung cancer cell lines was further analyzed for high quality RNA profiles using Illumina Hiseq2500. This series contains only RNA-seq data.
Project description:Response rates to immune checkpoint blockade (ICB) in ovarian cancer are low. In preclinical studies, poly(ADP-ribose) polymerase (PARP) inhibition synergized with CTLA4 ICB to achieve long-term survival in Brca1-deficient ovarian cancer models. Here, we evaluated the safety and efficacy of combined treatment with the PARP inhibitor olaparib and the CTLA4 ICB tremelimumab for recurrent epithelial ovarian cancer in a multi-site single-arm phase I/II study enrolling 50 women with a germline BRCA1 or BRCA2 mutation (NCT0257125). Grade 3 or 4 non-hematologic toxicity was reported in 57% of subjects, with tremelimumab discontinuation in 34.7%. The overall response rate was 32.7% (95% CI 19.5-45.8%), with a disease control rate of 47.7% (95% CI 33.0-62.5%). In exploratory biomarker analyses, low VSTM5 or IFIT1B expression was associated with treatment benefit and progression-free survival (p<0.001). Although this trial did not meet its prespecified efficacy endpoint, durable responses in some subjects in this heavily pre-treated cohort highlight the need for predictive biomarkers to select combinatorial regimens for patients with recurrent ovarian cancer.
Project description:Erlotinib is a tyrosine kinase inhibitor (TKI) that is approved as a second-line monotherapy in patients with advanced non-small cell lung cancer (NSCLC). In these patients, erlotinib prolongs survival but its benefit remains modest since overtime, many tumors develop resistance. To analyse the changes in the gene expression profile, that accompany resistance development, we treated the erlotinib sensitive non-small cell lung cancer cell line H358 with increasing concentrations of erlotinib (1-5µM) for several weeks (H358res). In parallel, we kept H358 with the same concentrations of the vehicle DMSO (H358co). After ten weeks of treatment, when the H358res stably grew under 5µM erlotinib, total RNA of both cell lines was harvested and hybridized.
Project description:Erlotinib is a tyrosine kinase inhibitor (TKI) that is approved as a second-line monotherapy in patients with advanced non-small cell lung cancer (NSCLC). In these patients, erlotinib prolongs survival but its benefit remains modest since overtime, many tumors develop resistance. To analyse the changes in the gene expression profile, that accompany resistance development, we treated the erlotinib sensitive non-small cell lung cancer cell line H358 with increasing concentrations of erlotinib (1-5µM) for several weeks (H358res). In parallel, we kept H358 with the same concentrations of the vehicle DMSO (H358co). After ten weeks of treatment, when the H358res stably grew under 5µM erlotinib, total RNA including microRNA of both cell lines was harvested and analyzed.