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  • 1
    Online Resource
    Online Resource
    CD8+ T Cell/Cancer-Associated Fibroblasts Ratio Stratifies Prognostic and Predictive Responses to Immunotherapy Across Multiple Cancer Types
    Elsevier BV ; 2022
    In:  SSRN Electronic Journal
    Details
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    URL: Article
    DOI: 10.2139/ssrn.4141239
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 2
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    Table_1.xls
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-9)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-9)
    Abstract: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8 + T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear. Materials and methods The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8 + T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort. Results Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman’s r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75; p & lt; 0.001). Conclusions CFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.974265
    DOI: 10.3389/fimmu.2022.974265.s001
    DOI: 10.3389/fimmu.2022.974265.s002
    DOI: 10.3389/fimmu.2022.974265.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    Cerebrospinal fluid circulating tumor DNA for the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e21039-e21039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e21039-e21039
    Abstract: e21039 Background: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. Methods: Patients with LM from NSCLC were retrospectively analyzed. Circulating tumor DNA (ctDNA) of CSFand pairedextracranial tissue or plasma were tested by ARMS or next-generation sequencing(NGS).Clinical outcomes were compared with Kaplan-Meier log-rank test and Coxproportional hazards methodologies. Results: We reviewed charts of 80 patients with LM treated atFujian Cancer Hospital. A total of 57 CSF and of which 30 contemporaneouslypaired extracranial samples tested by NGS were analyzed. Most interestingly, CSF ctDNA revealed EGFR mutations in 4 patients previously diagnosed as wild-type by extracranial specimens, and survival was extended by targeted therapy. In the gene map of paired samples, CSF showed more abundant cell-cycle regulatory genes and complex independent evolutionary. CDKN2A/2B CNVs-del was enriched threefold in CSF (~26.3%) with LM compared to extracranial specimens (~8.9%)in lung adenocarcinoma without LM. The median overall survival (OS) was 14.1 months [95% confidence interval (CI): 10.7–17.5 months]. Univariate analyses and multivariate Cox analyses demonstrated that patients with CDKN2A/CDKN2Bco-mutation had poor prognosis. Conclusions: CSF-based ctDNA testing contributes to the phenotypic detection and unique characterization of resistance mechanisms of LM in NSCLC. CDKN2A/2B mutation maybe a poor prognostic factor in LM patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e21039
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Online Resource
    A novel parameter reflecting the interaction between CD8+ T cells and cancer-associated fibroblasts.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e20536-e20536
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e20536-e20536
    Abstract: e20536 Background: Accumulating evidence reveal complicated crosstalk amongst cancer-related fibroblasts (CAFs) and immune cells in tumor microenvironment (TME). However, interaction within CAFs and immune cells, and their relationship with clinical outcomes remain largely undetermined. Methods: Interaction between CAFs and immune cells was evaluated by the CD8+ T cells/CAFs ratio (CFR), denoting great difference within single-sample gene-set enrichment analysis (ssGSEA) scores. Association of CFR with survival was examined in TCGA/GEO lung cancer and TCGA pan-cancer cohorts. Correlation between CFR and immunotherapeutic efficacy was determined in five independent cohorts including melanoma, lung cancer and urothelial cancer. orrelations between CFR and objective response rates (ORR) reported in the literature following pembrolizumab monotherapy were calculated in 20 TCGA cancer cohorts. To translate the in silico findings into clinical use, immunohistochemically-detected CD8/α-SMA ratio was used as prognostic and immuno-therapeutically predictive biomarker in two lung cancer cohorts. Furthermore, correlation within CFR, TMB, PD-L1, and molecular/genomic characteristics of CFR subgroups was also evaluated. Results: A moderately positive correlation existed between CAFs and immune cells infiltration in various cancer types. Higher immune cells/CAFs ratios indicated favorable prognosis regardless of distinct immune cells. Higher CFR, an independent risk factor and complementary factor to PD-L1 and TMB, was strongly associated with improved survival in melanoma, lung cancer and urothelial cancer immunotherapy cohorts (log-rank test, P 〈 0.05). Moreover, CFR averages across cancer types provided a higher correlation coefficient with the ORR following pembrolizumab monotherapy when compared to PD-L1 expression and TMB, r = 0.65 versus 0.36 and 0.31, respectively. Finally, in the clinical setting, CD8/α-SMA ratio was validated as an independent prognostic and predictive biomarker of immunotherapy efficacy in non-small cell lung cancer (HR, 0.21, 95% CI, 0.12-0.37, P 〈 0.001; HR, 0.37; 95% CI, 0.19-0.75; P 〈 0.001). Low CFR was associated with upregulation of hypoxia, TGF-β signaling, epithelial-mesenchymal transition and angiogenesis. Conclusions: CFR was a promising biomarker in the prediction of immunotherapeutic efficacy across various malignancies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e20536
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Interaction between CAF and CD8+ T cells in non-small cell lung cancer affects prognosis and efficacy of immunotherapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 9536-9536
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9536-9536
    Abstract: 9536 Background: Cancer-related fibroblasts (CAFs) are important components of the tumor microenvironment (TME) and play a key role in tumor progression. There is growing evidence that CAF levels in tumors are highly correlated with treatment response and prognosis. However, the effect of CAFs on immunotherapy response remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The SVA package ComBat function was used to remove batch effects. The ssGSEA algorithm was used to assess the level of cell infiltration in each sample. OS (overall survival) and DFS (disease free survival) were analyzed using the Kaplan–Meier method. GO enrichment analysis was used to assess the biological processes of subgroup differential genes. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict the clinical response to immune checkpoint blockade. Results: We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. The prognosis according to CD8+ T cells was not strong, but CD8+ T cells / fibroblasts (CFR) were significant protective prognostic factors [n = 1588; hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.56–0.78; P 〈 0.001]. Multivariate analysis revealed that the CFR was an independent prognostic biomarker. The TCGA pan-cancer cohort confirmed the widespread presence of CMIRP in cancer. We further defined the CFR high and CFR low subgroups. CFR high samples were enriched with immune activation pathways including T cell activation, cytolysis, and antigen presentation, while CFR low was associated with immunosuppression including activation of transforming growth factor β, epithelial-mesenchymal transition, and angiogenesis pathways. Finally, we combined TIDE and submap to speculate that CFR is a potential prognostic marker of immunotherapy for NSCLC. Conclusions: We proposed the term “CMIRP” to shed light on a more accurate assessment of immune status. CFR is a potential marker for prognosis and predictive efficacy of immunotherapy in NSCLC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.9536
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Online Resource
    Intrapulmonic Cavity or Necrosis on Baseline CT Scan Serves as an Efficacy Predictor of Anti-PD-(L)1 Inhibitor in Advanced Lung Squamous Cell Carcinoma
    Informa UK Limited ; 2021
    In:  Cancer Management and Research Vol. Volume 13 ( 2021-07), p. 5931-5939
    Details
    In: Cancer Management and Research, Informa UK Limited, Vol. Volume 13 ( 2021-07), p. 5931-5939
    Type of Medium: Online Resource
    ISSN: 1179-1322
    URL: Article
    DOI: 10.2147/CMAR.S319480
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2508013-1
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  • 7
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    Online Resource
    Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer
    Elsevier BV ; 2023
    In:  European Journal of Cancer Vol. 188 ( 2023-07), p. 81-89
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 188 ( 2023-07), p. 81-89
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2023.04.009
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 8
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    Online Resource
    Tumor response heterogeneity, a powerful independent predictor of treatment outcome in advanced lung adenocarcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e21146-e21146
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21146-e21146
    Abstract: e21146 Background: Tumor response heterogeneity (TRH) to treatment is common across different foci within the same cancer patient. However, the effect of heterogeneity on clinical outcome remains unclear. Here, we developed a quantitative assessment of TRH and explored the correlation of TRH with the clinical outcome. Methods: In this retrospective study, the main eligibility criteria were: patients with advanced lung adenocarcinoma, 3-10 measured foci, ECOG 0-1 and received first-line chemotherapy or targeted therapy. Percent change of the longest diameter in each measurable lesion were quantified with RECIST1.1. TRH score was the absolute value of the dispersion coefficient of the percentage value of each target lesion. Patients were randomly divided into a learning and a validation set. The optimal cutoff value of TRH score was identified according to progression free survival information in the discovery cohort. Then, we confirmed and analyzed the correlation of TRH scores with clinicopathological features in the validation cohort. The Next-generation sequencing was performed for mechanism exploration. Results: Between January 2016 and December 2020, 174 patients were enrolled, 101 (58.0%) treated with platinum-based doublet chemotherapy and 73 (42.0%) with targeted therapy. Median follow-up was 19.8 months (95% CI, 14.5 to 25.0). In the discovery cohort (n = 85), 0.46 was defined as the optimal cut-off point of TRH score. Patients with high TRH score had poor PFS (median PFS 4.5 months vs. 15.8 months, HR 4.43; 95% CI 2.14 to 9.16; P 〈 0.001) compared to those with low TRH score. In validation cohort (n = 89), high TRH score was confirmed to be associated with significantly shorter PFS (median PFS 5.1 months vs. 12.9 months, HR 2.69; 95% CI 1.59 to 4.55; P 〈 0.001). The median value of TRH score followed the order of PD, SD and PR ( P 〈 0.001). Patients with high TRH score had poor ORR (30.0% vs. 68.0%; Fisher's exact test, P 〈 0.001) compared with those with low TRH score. In all population, high TRH score was further confirmed as an independent biomarker for PFS by univariate and multivariate analysis. Moreover, TRH score were able to further distinguish the outcomes in PR and SD subgroup. In PR, high TRH score was associated with significantly shorter PFS in PR subgroup (HR 2.79; 95% CI 1.24 to 6.29; P 〈 0.001) and SD subgroup (HR 2.55; 95% CI 1.44 to 4.49; P = 0.002), respectively. Compared with low TRH score, high TRH score was associated with higher tumor mutation burden and high frequency variation of cell cycle signal pathway. Conclusions: TRH score, a novel parameter for evaluating tumor response heterogeneity, was a powerful independent predictor of outcome in advanced lung adenocarcinoma. The TRHscore further stratifies patients with the same RECIST assessment results and is a useful addition to the RECIST assessment system. Further prospective studies are warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e21146
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Online Resource
    Tumour response heterogeneity as a powerful independent predictor of treatment outcome in advanced lung adenocarcinoma: a retrospective analysis
    Elsevier BV ; 2022
    In:  The Lancet Oncology Vol. 23 ( 2022-07), p. S13-
    Details
    In: The Lancet Oncology, Elsevier BV, Vol. 23 ( 2022-07), p. S13-
    Type of Medium: Online Resource
    ISSN: 1470-2045
    URL: Article
    DOI: 10.1016/S1470-2045(22)00412-0
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2049730-1
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  • 10
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-12)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-12)
    Abstract: Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T-cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. Twenty-two (73.3%) patients were EGFR-positive. The TIME was defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) were predominantly expressed in squamous cell carcinoma components (SCCCs) versus adenocarcinoma components (ACCs), where enhanced CD4 + FOXP3 + regulatory T cell and attenuated CD57 + natural killer cell infiltration were present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCCs had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort III, the efficacy of ICI-based therapy was estimated using a real-world data of 46 ASCs from 11 centers. Majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. The overall objective response rate of 28%, median progression-free survival of 6.0 months (95% confidence interval [CI] 4.3–7.7), and median overall survival of 24.7 months (95% CI 7.2–42.2) were observed in the ICI-based treatment. This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACCs and SCCCs. Lung ASC patients have a moderate response to ICI-based immunotherapy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.944812
    DOI: 10.3389/fimmu.2022.944812.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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