Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biomarkers of immunotherapy in non-small cell lung cancer.

ABSTRACT: Immunotherapy has markedly improved the survival rate of patients with non-small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. However, not all patients with lung cancer benefit from checkpoint blockade, and some suffer from notable immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Based on the current clinical trials, the aim of the present study was to review the biomarkers for immune checkpoint inhibition, as well as other effective, invalid and hyperprogression markers that may have the potential to better predict responders to immunotherapy among patients with NSCLC. All these biomarkers may be incorporated into the predictive utility of bio-score systems and decision-making algorithms, to better guide the application of immunotherapy in the clinical setting.

SUBMITTER: Wang L

PROVIDER: S-EPMC7471728 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Biomarkers of immunotherapy in non-small cell lung cancer.

Wang Lingling L Hu Yue Y Wang Shengchao S Shen Jiali J Wang Xiaochen X

Oncology letters 20200820 5

Immunotherapy has markedly improved the survival rate of patients with non-small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. However, not all patients with lung cancer benefit from checkpoint blockade, and some suffer from notable immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Based on the current clinical trials, the aim of the present study was to review the bi ...[more]

PMID: 32934707

Similar Datasets

Combining Genomic Biomarkers to Guide Immunotherapy in Non-Small Cell Lung Cancer.

Project description:PurposeThe clinical value of STK11, KEAP1, and EGFR alterations for guiding immune checkpoint blockade (ICB) therapy in non-small cell lung cancer (NSCLC) remains controversial, as some patients with these proposed resistance biomarkers show durable ICB responses. More specific combinatorial biomarker approaches are urgently needed for this disease.Experimental designTo develop a combinatorial biomarker strategy with increased specificity for ICB unresponsiveness in NSCLC, we performed a comprehensive analysis of 254 patients with NSCLC treated with ligand programmed death-ligand 1 (PD-L1) blockade monotherapy, including a discovery cohort of 75 patients subjected to whole-genome sequencing (WGS), and an independent validation cohort of 169 patients subjected to tumor-normal large panel sequencing. The specificity of STK11/KEAP1/EGFR alterations for ICB unresponsiveness was assessed in the contexts of a low (<10 muts/Mb) or high (≥10 muts/Mb) tumor mutational burden (TMB).ResultsIn low TMB cases, STK11/KEAP1/EGFR alterations were highly specific biomarkers for ICB resistance, with 0/15 (0.0%) and 1/34 (2.9%) biomarker-positive patients showing treatment benefit in the discovery and validation cohorts, respectively. This contrasted with high TMB cases, where 11/13 (85%) and 15/34 (44%) patients with at least one STK11/KEAP1/EGFR alteration showed durable treatment benefit in the discovery and validation cohorts, respectively. These findings were supported by analyses of progression-free survival and overall survival.ConclusionsThe unexpected ICB responses in patients carrying resistance biomarkers in STK11, KEAP1, and EGFR were almost exclusively observed in patients with a high TMB. Considering these alterations in context, the TMB offered a highly specific combinatorial biomarker strategy for limiting overtreatment in NSCLC.

| S-EPMC10982639 | biostudies-literature

Current and future biomarkers for outcomes with immunotherapy in non-small cell lung cancer.

Project description:Immune checkpoint inhibitors (ICI) have been validated as an effective new treatment strategy in several tumoral types including lung cancer. This remarkable shift in the therapeutic paradigm is in large part due to the duration of responses and long-term survival seen with ICI. However, despite this, the majority of cancer patients do not experience benefit from ICI. Even among patients who initially respond to ICI, disease progression may ultimately occur. Moreover, in some patients, these drugs may be associated with new patterns of progression such as pseudo-progression and hyper-progressive disease, and different toxicity profiles with immune-related adverse events. Therefore, the identification of predictive biomarkers may help to select those patients most likely to obtain a true benefit from these drugs, and avoid exposure to potential toxicity in patients who will not obtain clinical benefit, while also reducing the economic impact. In this review, we summarize current and promising potential predictive biomarkers of ICI in patients with non-small cell lung cancer (NSCLC), as well as pitfalls encountered with their use and areas of focus to optimize their routine clinical implementation.

| S-EPMC8264336 | biostudies-literature

Targeted immunotherapy for non-small cell lung cancer.

Project description:Targeted therapies that deliver the expected anti-tumor effects while mitigating the adverse effects are taking the cancer world by storm. The need for such therapies in non-small cell lung cancer (NSCLC), where systemic cytotoxic chemotherapies still remain the backbone of management, is felt more than ever before. Runway success of immunotherapies such as Ipilimumab for melanoma has brought excitement among oncologists. Immune-based treatments are in various stages of evaluation for NSCLC as well. Immunotherapies using strategies of antigen based or cell based vaccines, and blocking immune checkpoints are of substantial interest. Meaningful clinical responses are yet to be reaped from these new treatment modalities.

| S-EPMC4014795 | biostudies-literature

Research progress of extracellular vesicles as biomarkers in immunotherapy for non-small cell lung cancer.

Project description:Lung cancer is one of the most severe forms of malignancy and a leading cause of cancer-related death worldwide, of which non-small cell lung cancer (NSCLC) is the most primary type observed in the clinic. NSCLC is mainly treated with surgery, radiotherapy, and chemotherapy. Additionally, targeted therapy and immunotherapy have also shown promising results. Several immunotherapies, including immune checkpoint inhibitors, have been developed for clinical use and have benefited patients with NSCLC. However, immunotherapy faces several challenges like poor response and unknown effective population. It is essential to identify novel predictive markers to further advance precision immunotherapy for NSCLC. Extracellular vesicles (EVs) present an important research direction. In this review, we focus on the role of EVs as a biomarker in NSCLC immunotherapy considering various perspectives, including the definition and properties of EVs, their role as biomarkers in current NSCLC immunotherapy, and different EV components as biomarkers in NSCLC immunotherapy research. We describe the cross-talk between the role of EVs as biomarkers and novel technical approaches or research concepts in NSCLC immunotherapy, such as neoadjuvants, multi-omics analysis, and the tumour microenvironment. This review will provide a reference for future research to improve the benefits of immunotherapy for patients with NSCLC.

| S-EPMC10162406 | biostudies-literature

Active-specific immunotherapy for non-small cell lung cancer.

Project description:Non-small cell lung cancer constitutes about 85% of all newly diagnosed cases of lung cancer and continues to be the leading cause of cancer-related deaths worldwide. Standard treatment for this devastating disease, such as systemic chemotherapy, has reached a plateau in effectiveness and comes with considerable toxicities. For all stages of disease fewer than 20% of patients are alive 5 years after diagnosis; for metastatic disease the median survival is less than one year. Until now, the success of active-specific immunotherapy for all tumor types has been sporadic and unpredictable. However, the active-specific stimulation of the host's own immune system still holds great promise for achieving non-toxic and durable antitumor responses. Recently, sipuleucel-T (Provenge(®); Dendreon Corp., Seattle, WA) was the first therapeutic cancer vaccine to receive market approval, in this case for advanced prostate cancer. Other phase III clinical trials using time-dependent endpoints, e.g. in melanoma and follicular lymphoma, have recently turned out positive. More sophisticated specific vaccines have now also been developed for lung cancer, which, for long, was not considered an immune-sensitive malignancy. This may explain why advances in active-specific immunotherapy for lung cancer lag behind similar efforts in renal cell cancer, melanoma or prostate cancer. However, various vaccines are now being evaluated in controlled phase III clinical trials, raising hopes that active-specific immunotherapy may become an additional effective therapy for patients with lung cancer. This article reviews the most prominent active-specific immunotherapeutic approaches using protein/peptide, whole tumor cells, and dendritic cells as vaccines for lung cancer.

| S-EPMC3256502 | biostudies-literature

Neoadjuvant immunotherapy for resectable non-small cell lung cancer.

Project description:Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. In recent ten years, with the emergence of new drugs and the optimization of treatment mode, the treatment of lung cancer is entering an era of precision and individualization. Neoadjuvant therapy can reduce tumor size, degrade tumor stage, kill circulating tumor cells and micrometastases in the body, afford operation possibility, and benefit the long-term survival of patients. However, the traditional neoadjuvant chemotherapy combined with surgical treatment seems to have entered the bottleneck period of efficacy and is difficult to achieve breakthrough progress. At the same time, the amazing efficacy of immunotherapy is gradually innovating the treatment mode of lung cancer. In recent years, the research data of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) shows an explosive growth. Immunotherapy has been applied to the first-line treatment of advanced NSCLC. Therefore, some clinical trials have applied immunotherapy to neoadjuvant treatment of resectable NSCLC patients. In this paper, the efficacy, possible mechanisms, potential risks and existing problems of neoadjuvant immunotherapy for resectable NSCLC patients are reviewed, and the future development direction of neoadjuvant immunotherapy is discussed.

| S-EPMC8263648 | biostudies-literature

Neoadjuvant immunotherapy in resectable non-small-cell lung cancer.

Project description:The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT. Significant interest in neoadjuvant chemoimmunotherapy resulted in the conduct of multiple successful phase II trials including the Columbia trial, NADIM, SAKK 16/14, and NADIM II. Across these trials, neoadjuvant chemoimmunotherapy led to high rates of pathologic response and improved surgical outcomes without compromising surgical timing or feasibility. CheckMate-816, which was a randomized phase III trial studying neoadjuvant nivolumab in addition to chemotherapy, definitively established a benefit for neoadjuvant chemoimmunotherapy compared to chemotherapy alone for resectable NSCLC. Despite the growing literature and success of these trials, several outstanding questions remain, including the relationship between pathologic response and patient survival, the role of biomarkers such as programmed death ligand 1 and circulating tumor DNA in determining patient selection and treatment course, and the utility of additional adjuvant therapies. Longer follow-up of CheckMate-816 and other ongoing phase III trials may help address these questions. Ultimately, the complexity of managing resectable NSCLC highlights the importance of a multidisciplinary approach to patient care.

| S-EPMC10052589 | biostudies-literature

Immunotherapy in surgically resectable non-small cell lung cancer.

Project description:Surgical resection is the mainstay of therapy for patients with resectable and operable early stage non-small cell lung cancer (NSCLC). Surgery alone yields an unacceptably high rate of lung cancer recurrence. The addition of chemotherapy to surgery as adjuvant or neoadjuvant treatment can improve survival rates by roughly 5% at 5 years. Recently, major advances in cancer immunotherapy have led to better outcomes for many patients with lung cancer. Monoclonal antibodies to programmed death 1 and its ligand are now approved for both first and second line treatment patients with metastatic lung cancer. In this review, we will outline the rationale and current research strategies investigating the role of immunotherapy in resectable NSCLC.

| S-EPMC5861266 | biostudies-literature

Immunotherapy combination strategies (non-chemotherapy) in non-small cell lung cancer.

Project description:Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results. The PD1 inhibitors such as pembrolizumab have now received FDA approval in the first-line setting for patients with positive PD-L1 expression tumor types; however, only a portion of patients have shown objective and sustainable responses. To expand the number of patients with observed response to immunotherapeutic agents including patients with negative PD-L1 expression tumors, clinical trials are ongoing to assess the safety and efficacy of combination immune checkpoint inhibitors and combination immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors have been found to be a promising therapeutic drug class with sustainable response rates and a tolerable safety profile, and efforts continue to improve these drugs in patients with NSCLC.

| S-EPMC5861267 | biostudies-literature

CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer.

Project description:ObjectivePrecision immunotherapy in non-small cell lung cancer (NSCLC) have been the focus of tumor immunity research. The aim of this study is to identify novel candidate biomarkers predicting the response to immunotherapy in NSCLC.MethodsGSE126044 was obtained from Gene Expression Omnibus (GEO). According to the response to anti-PD-1 antibody, 2 groups were divided: response group and non-response group. Differentially expressed genes (DEGs) were screened using R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. ROC curves and possible pathways of the seed genes were further analyzed.ResultsIn total, 588 DEGs (487 upregulated DEGs and 101 downregulated) were identified. GO and KEGG analyses showed that upregulated DEGs were mainly enriched in immune response and cell adhesion pathways, while VEGF signaling pathway and metabolic pathways were mainly enriched in downregulated DEGs. In addition, CSF1 R and HCST showed more powerful predictive ability than PDL1. More importantly, these candidate genes were not only positively correlated with the expression of PDL1 and the infiltration of CD8+ T cells in the immune microenvironment, but also might improve the prognosis in lung squamous cell carcinoma.ConclusionsCSF1 R and HCST might be novel predictive markers for immunotherapy in NSCLC.

| S-EPMC7658512 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data