Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cellular and molecular immunology of lung cancer: therapeutic implications.

ABSTRACT: Although the incidence of lung cancer is declining, the prognosis remains poor. This is likely due to lack of early detection and only recent developments in selective cancer therapies. Key immune cells involved in the pathogenesis of lung cancer include CD4(+) T lymphocytes, macrophages, dendritic cells and NK cells. The growing understanding of these cells indicates a highly complex and intertwined network of their involvement in each stage of lung cancer. Immune cell types and numbers affect prognosis and could offer an opportunity for clinical therapeutic applications. However, an incomplete understanding of immune cell involvement and the underlying processes in lung cancer still remain. Deeper investigation focusing on the role of the immune cells will further the understanding of lung carcinogenesis and develop novel therapeutic approaches for the treatment and management of patients with more specialized and selective lung cancer.

SUBMITTER: Nguyen AH

PROVIDER: S-EPMC4596236 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Cellular and molecular immunology of lung cancer: therapeutic implications.

Nguyen Austin Huy AH Berim Ilya G IG Agrawal Devendra K DK

Expert review of clinical immunology 20141028 12

Although the incidence of lung cancer is declining, the prognosis remains poor. This is likely due to lack of early detection and only recent developments in selective cancer therapies. Key immune cells involved in the pathogenesis of lung cancer include CD4(+) T lymphocytes, macrophages, dendritic cells and NK cells. The growing understanding of these cells indicates a highly complex and intertwined network of their involvement in each stage of lung cancer. Immune cell types and numbers affect ...[more]

PMID: 25351434

Similar Datasets

Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications.

Project description:Prostate cancer is the most frequent nonskin cancer and second most common cause of cancer-related deaths in man. Prostate cancer is a clinically heterogeneous disease with many patients exhibiting an aggressive disease with progression, metastasis, and other patients showing an indolent disease with low tendency to progression. Three stages of development of human prostate tumors have been identified: intraepithelial neoplasia, adenocarcinoma androgen-dependent, and adenocarcinoma androgen-independent or castration-resistant. Advances in molecular technologies have provided a very rapid progress in our understanding of the genomic events responsible for the initial development and progression of prostate cancer. These studies have shown that prostate cancer genome displays a relatively low mutation rate compared with other cancers and few chromosomal loss or gains. The ensemble of these molecular studies has led to suggest the existence of two main molecular groups of prostate cancers: one characterized by the presence of ERG rearrangements (~50% of prostate cancers harbor recurrent gene fusions involving ETS transcription factors, fusing the 5' untranslated region of the androgen-regulated gene TMPRSS2 to nearly the coding sequence of the ETS family transcription factor ERG) and features of chemoplexy (complex gene rearrangements developing from a coordinated and simultaneous molecular event), and a second one characterized by the absence of ERG rearrangements and by the frequent mutations in the E3 ubiquitin ligase adapter SPOP and/or deletion of CDH1, a chromatin remodeling factor, and interchromosomal rearrangements and SPOP mutations are early events during prostate cancer development. During disease progression, genomic and epigenomic abnormalities accrued and converged on prostate cancer pathways, leading to a highly heterogeneous transcriptomic landscape, characterized by a hyperactive androgen receptor signaling axis.

| S-EPMC6789661 | biostudies-literature

Molecular profiles of small cell lung cancer subtypes: therapeutic implications.

Project description:Small cell lung cancer (SCLC; accounting for approximately 13%-15% of all lung cancers) is an exceptionally lethal malignancy characterized by rapid doubling time and high propensity to metastasize. In contrast to the increasingly personalized therapies in other types of lung cancer, SCLC is still regarded as a homogeneous disease and the prognosis of SCLC patients remains poor. Recently, however, substantial progress has been made in our understanding of SCLC biology. Advances in genomics and development of new preclinical models have facilitated insights into the intratumoral heterogeneity and specific genetic alterations of this disease. This worldwide resurgence of studies on SCLC has ultimately led to the development of novel subtype-specific classifications primarily based on the neuroendocrine features and distinct molecular profiles of SCLC. Importantly, these biologically distinct subtypes might define unique therapeutic vulnerabilities. Herein, we summarize the current knowledge on the molecular profiles of SCLC subtypes with a focus on their potential clinical implications.

| S-EPMC7917449 | biostudies-literature

Lung cancer in never smokers: molecular profiles and therapeutic implications.

Project description:The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. Although a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years show that lung cancers in never smokers are much more likely to carry activating mutations of the epidermal growth factor receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anticancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never-smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers.

| S-EPMC2950319 | biostudies-literature

Exploring natural killer cell immunology as a therapeutic strategy in lung cancer.

Project description:Cytotoxic immune cells are key in the control of tumor development and progression. Natural killer (NK) cells are the cytotoxic arm of the innate immune system with the capability to kill tumor cells and surveil tumor cell dissemination. As such, the interest in harnessing NK cells in tumor control is increasing in many solid tumor types, including lung cancer. Here, we review the pre-clinical models used to unveil the role of NK cells in immunosurveillance of solid tumors and highlight measures to enhance NK cell activity. Importantly, the development of NK immunotherapy is rapidly evolving. Enhancing the NK cell response can be achieved using two broad modalities: enhancing endogenous NK cell activity, or performing adoptive transfer of pre-activated NK cells to patients. Numerous clinical trials are evaluating the efficacy of NK cell immunotherapy in isolation or in combination with standard treatments, with encouraging initial results. Pre-clinical studies and early phase clinical trials suggest that patients with solid tumors, including lung cancer, have the potential to benefit from recent developments in NK cell immunotherapy.

| S-EPMC8264324 | biostudies-literature

Pan-cancer illumination of TRIM gene family reveals immunology regulation and potential therapeutic implications.

Project description:BackgroundThe tripartite motif (TRIM) proteins function as important regulators in innate immunity, tumorigenesis, cell differentiation and ontogenetic development. However, we still lack knowledge about the genetic and transcriptome alterations landscape of TRIM proteins across cancer types.MethodsWe comprehensively reviewed and characterized the perturbations of TRIM genes across > 10,000 samples across 33 cancer types. Genetic mutations and transcriptome of TRIM genes were analyzed by diverse computational methods. A TRIMs score index was calculated based on the expression of TRIM genes. The correlation between TRIMs scores and clinical associations, immune cell infiltrations and immunotherapy response were analyzed by correlation coefficients and gene set enrichment analysis.ResultsAlterations in TRIM genes and protein levels frequently emerge in a wide range of tumors and affect expression of TRIM genes. In particular, mutations located in domains are likely to be deleterious mutations. Perturbations of TRIM genes are correlated with expressions of immune checkpoints and immune cell infiltrations, which further regulated the cancer- and immune-related pathways. Moreover, we proposed a TRIMs score index, which can accurately predict the clinical outcome of cancer patients. TRIMs scores of patients are correlated with clinical survival and immune therapy response across cancer types. Identifying the TRIM genes with genetic and transcriptome alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.ConclusionsOur study provided a comprehensive analysis and resource for guiding both mechanistic and therapeutic analyses of the roles of TRIM genes in cancer.

| S-EPMC9719184 | biostudies-literature

The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer.

Project description:Cancer immunotherapy has been heralded as a breakthrough cancer treatment demonstrating tremendous success in improving tumor responses and survival of patients with hematological cancers and solid tumors. This novel promising treatment approach has in particular triggered optimism for triple negative breast cancer (TNBC) treatment, a subtype of breast cancer with distinct clinical features and poor clinical outcome. In early 2019, the FDA granted the first approval of immune checkpoint therapy, targeting PD-L1 (Atezolizumab) in combination with chemotherapy for the treatment of patients with locally advanced or metastatic PD-L1 positive TNBC. The efficacy of immuno-based interventions varies across cancer types and patient cohorts, which is attributed to a variety of lifestyle, clinical, and pathological factors. For instance, obesity has emerged as a risk factor for a dampened anti-tumor immune response and increased risk of immunotherapy-induced immune-related adverse events (irAEs) but has also been linked to improved outcomes with checkpoint blockade. Given the breadth of the rising global obesity epidemic, it is imperative to gain insight into the immunomodulatory effects of obesity in the peripheral circulation and within the tumor microenvironment. In this review, we resolve the impact of obesity on breast tumorigenesis and progression on the one hand, and on the immune contexture on the other hand. Finally, we speculate on the potential implications of obesity on immunotherapy response in breast cancer. This review clearly highlights the need for in vivo obese cancer models and representative clinical cohorts for evaluation of immunotherapy efficacy.

| S-EPMC6703078 | biostudies-literature

Cellular determinants and therapeutic implications of inflammation in pancreatic cancer.

Project description:Inflammation is a hallmark of cancer. For pancreatic ductal adenocarcinoma (PDAC), malignant cells arise in the context of a brisk inflammatory cell infiltrate surrounded by dense fibrosis that is seen beginning at the earliest stages of cancer conception. This inflammatory and fibrotic milieu supports cancer cell escape from immune elimination and promotes malignant progression and metastatic spread to distant organs. Targeting this inflammatory reaction in PDAC by inhibiting or depleting pro-tumor elements and by engaging the potential of inflammatory cells to acquire anti-tumor activity has garnered strong research and clinical interest. Herein, we describe the current understanding of key determinants of inflammation in PDAC; mechanisms by which inflammation drives immune suppression; the impact of inflammation on metastasis, therapeutic resistance, and clinical outcomes; and strategies to intervene on inflammation for providing therapeutic benefit.

| S-EPMC6708742 | biostudies-literature

Molecular Mechanism for Cellular Response to β-Escin and Its Therapeutic Implications.

Project description:β-escin is a mixture of triterpene saponins isolated from the horse chestnut seeds (Aesculus hippocastanum L.). The anti-edematous, anti-inflammatory and venotonic properties of β-escin have been the most extensively clinically investigated effects of this plant-based drug and randomized controlled trials have proved the efficacy of β-escin for the treatment of chronic venous insufficiency. However, despite the clinical recognition of the drug its pharmacological mechanism of action still remains largely elusive. To determine the cellular and molecular basis for the therapeutic effectiveness of β-escin we performed discovery and targeted proteomic analyses and in vitro evaluation of cellular and molecular responses in human endothelial cells under inflammatory conditions. Our results demonstrate that in endothelial cells β-escin potently induces cholesterol synthesis which is rapidly followed with marked fall in actin cytoskeleton integrity. The concomitant changes in cell functioning result in a significantly diminished responses to TNF-α stimulation. These include reduced migration, alleviated endothelial monolayer permeability, and inhibition of NFκB signal transduction leading to down-expression of TNF-α-induced effector proteins. Moreover, the study provides evidence for novel therapeutic potential of β-escin beyond the current vascular indications.

| S-EPMC5058498 | biostudies-literature

Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.

Project description:Breast cancer stem cells (BCSCs) constitute a small population of cells within breast cancer and are characterized by their ability to self-renew, differentiate, and recapitulate the heterogeneity of the tumor. Clinically, BCSCs have been correlated with cancer progression, metastasis, relapse, and drug resistance. The tumorigenic roles of BCSCs have been extensively reviewed and will not be the major focus of the current review. Here, we aim to highlight how the crucial intrinsic signaling pathways regulate the fate of BCSCs, including the Wnt, Notch, Hedgehog, and NF-κB signaling pathways, as well as how different cell populations crosstalk with BCSCs within the TME, including adipocytes, endothelial cells, fibroblasts, and immune cells. Based on the molecular and cellular activities of BCSCs, we will also summarize the targeting strategies for BCSCs and related clinical trials. This review will highlight that BCSC development in breast cancer is impacted by both BCSC endogenous signaling and external factors in the TME, which provides an insight into how to establish a comprehensively therapeutic strategy to target BCSCs for breast cancer treatments.

| S-EPMC9265870 | biostudies-literature

Emerging molecular classifications and therapeutic implications for gastric cancer.

Project description:Gastric cancer (GC) is a highly aggressive and life-threatening malignancy. Even with radical surgical removal and front-line chemotherapy, more than half of GCs locally relapse and metastasize at a distant site. The dismal outcomes reflect the ineffectiveness of a one-size-fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings. The recent comprehensive genomic and molecular profiling has led to our deepened understanding of GC. The emerging molecular classification schemes based on the genetic, epigenetic, and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner. To this end, the Cancer Genome Atlas (TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes: Epstein-Barr virus-associated tumors, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. This review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy strategies. We believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs.

| S-EPMC4896142 | 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