Immunologically hot phenotype is associated with response to second-line PD-1/PD-L1 inhibition in patients with advanced non-small cell lung cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE161537 | GEO | 2022/07/07
REPOSITORIES: GEO
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Project description:Ongoing immunomodulatory strategies in tumors characterized by an overall hot immune phenotype may improve prognosis of head and neck squamous cell carcinomas (HNSCC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically hot HNSCC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas. HOT score was computed in 102 patients with HNSCC treated with immunotherapy targeting PD-1/PD-L1 in the context of clinical trials. High HOT score was associated with a statistically significant improved clinical outcome.
2022-07-07 | GSE159067 | GEO
Project description:Immunotherapy in immunologically active tumors may improve prognosis of non-small cell lung carcinomas (NSCLC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically active HNSCC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas in human-papillomavirus negative head and neck squamous cell carcinomas; it was computed in 92 patients with early stage NSCLC treated with surgery to evaluate the prognostic impact of the HOT score.
2022-07-07 | GSE162520 | GEO
Project description:Lung cancer is a major global health problem, as it is the leading cause of cancer- related deaths worldwide. Non-small-cell lung cancer (NSCLC), the most common form, is a heterogeneous disease with adenocarcinoma and squamous cell carcinoma being the predominant subtypes. Immune-inhibiting interaction of Programmed cell death-ligand 1 (PD-L1) with programmed cell death-protein 1 (PD-1) causes checkpoint mediated immune evasion and is, accordingly, an important therapeutic target in cancer. In NSCLC, improved understanding of PD-1/PD-L1 checkpoint blockade-responsive biology is warranted. We aimed to identify the landscape of immune cell infiltration in primary lung adeno- carcinoma (LUAD) in the context of tumor PD-L1 expression and the extent of immune infiltration (“hot” vs. “cold” phenotype). Therefore, the study comprises LUAD cases (n=138) with “hot” and “cold” tumor immune phenotype and positive and negative tumor PD-L1 expression, respectively. Tumor samples were immunohistochemically analyzed for expression of PD-L1, CD4 and CD8 and further analyzed on transcriptomic level by Nanostring nCouter Pan Cancer Immune Profiling Panel. We detected significantly differentially expressed genes associated with PD-L1 positive and “hot” versus PD-L1 negative and “cold” phenotype. The presented study illustrates novel aspects of PD-L1 regulation, with potential biological relevance, as well as relevance for immunotherapy response stratification.
2021-09-27 | GSE180347 | GEO
Project description:Ongoing immunomodulatory strategies in tumors characterized by an overall hot immune phenotype may improve prognosis of head and neck squamous cell carcinomas (HNSCC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically hot HNSCC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas. HOT score was then computed in 27 patients with HNSCC in paired perendoscopic tumor biopsy (initial diagnostic assessment) and subsequent surgically resected specimen. None of the patients was treated with neoadjuvant therapy. Concordance and correlation of the HOT score was high in paired samples.
2022-07-07 | GSE159141 | GEO
Project description:Immunologically hot phenotype is associated with response to second-line PD-1/PD-L1 inhibition in patients with advanced non-small cell lung cancer
| PRJNA678660 | ENA
Project description:Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.
2016-10-11 | GSE84789 | GEO
Project description:Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. 29 NSCLC cases analyzed wth Nanostring human PanCancer immune module
2016-10-11 | GSE84797 | GEO
Project description:Immunologically hot phenotype is associated with response to PD-1/PD-L1 inhibitors in patients with advanced head and neck squamous cell carcinoma.
| PRJNA667509 | ENA
Project description:BACKGROUND. Precise stratification of patients with non–small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy. METHODS. We measured soluble (s) forms of the PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. Prospective biomarker finding trial (cohort A), 50 patients with pretreated NSCLC received nivolumab. In cohort B to E, retrospective observational study, soluble immune checkpoint molecules were evaluated for patients with advanced NSCLC treated with any PD-1/PD-L1 blockade (cohort B and C), cytotoxic chemotherapy (D) or targeted therapy (E). Blood samples were obtained from all patients and soluble immune checkpoint molecules were evaluated using a highly sensitive chemiluminescence-based assay. RESULTS. Nonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such correlation was not observed in patients treated with cytotoxic chemotherapy or targeted therapies. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the three soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of sPD-L1 and sCTLA-4 efficiently discriminated responsiveness among patients with immune-reactive tumors. CONCLUSION. Combinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest such a combination might provide a biomarker complementary to tPD-L1 for NSCLC patients.
2024-03-30 | GSE242860 | GEO
Project description:Lack of a standard method for stratifying advanced-stage NSCLC patients receiving platinum combination therapy often results in a number of patients that do not derive benefit yet are still exposed to treatment toxicity. We hypothesized that miRNAs in pre-treatment serum and/or plasma could be used to differentiate non-small cell lung cancer (NSCLC) patients who would have disease progression to first-line carboplatin and gemcitabine chemotherapy at first response assessment. miRNA profiling of mature and precursor miRNAs was performed on total RNA isolated from the pre-treatment serum and plasma of 24 NSCLC patients. Single validated candidates or combinations thereof were selected based on specificity and sensitivity to segregate patients with disease progression at first radiologic response (PD) vs. those without progressed disease (nonPD). Two precursor miRNA were significantly over-expressed in serum (but not plasma) of PD patients: pre-miR-518b and pre-miR-598. Serum miRNAs may serve as a screening tool in predicting chemoresistance to platinum-based combination chemotherapy. miRNA microarray was performed on RNA extracted from matched human serum or plasma obtained from NSCLC patients
2012-12-01 | E-GEOD-25019 | biostudies-arrayexpress