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  • 1
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    Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 18 ( 2016-11-03), p. 2199-2205
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 18 ( 2016-11-03), p. 2199-2205
    Abstract: Toxicity was the most common reason for discontinuation of ibrutinib or idelalisib in treated patients with CLL. KI-intolerant patients, but less so those with CLL progression, can be successfully treated with an alternate KI.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2016-05-716977
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
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    Expression and clinical significance of antigen presentation components beta-2 microglobulin, HLA class I heavy chains, and HLA class II in non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 12015-12015
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 12015-12015
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.12015
    RVK:
    XA 52760
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    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 3
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    Effects of mutations in SWI/SNF subunits on context-specific prognosis in driver positive and driver negative NSCLC.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9039-9039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9039-9039
    Abstract: 9039 Background: Mutations(mt) in the Switch/Sucrose-Nonfermentable chromatin remodeling complex (SWI/SNF) are commonly found in NSCLC and have been associated with worse prognosis. However, the overall prognostic role of the individual SWI/SNF subunits in all NSCLCs and in oncogenic driver-positive (D+) and driver-negative (D-) groups remains unclear. Our study attempts to clarify the prognostic role of SWI/SNF subunit alterations in these populations. Methods: 42,379 NSCLC tumor specimens were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing (NGS) of DNA (592-gene panel or whole-exome sequencing). Based on the observed frequency of likely pathogenic/pathogenic (LP/P) mts, the four most commonly-altered SWI/SNF subunits – ARID1A (8.29%), SMARCA4 (6.29%), ARID2 (3.05%) and PBRM1 (1.98%) – were further analyzed. We divided the cohort by driver mts. D+ tumors possessed at least one of the following alterations: LP/P mts in KRAS, EGFR, BRAF, ERBB2 or MET; METex14 skipping; ERBB2 amplification, LP/P fusions in ALK (including IHC overexpression), RET, ROS1, NTRK (1-3) & NRG1. D- tumors were devoid of mts/amplifications/fusions in all genes mentioned above. Kaplan-Meier analysis was performed on real world survival data (n = 24685) obtained from insurance claims. Statistical significance was determined using chi-square and Mann-Whitney U test adjusted for multiple comparisons (q 〈 0.05). Results: Of the SWI/SNF genes, only SMARCA4mts were associated with worse survival in the overall (HR = 1.46), D+ (HR = 1.984) and D- (HR = 1.224) cohorts (all p 〈 0.01). While SMARCA4mt was associated in the D- cohort with KEAP1 and STK11 mts, the worse prognosis persisted even in their absence (HR = 1.41, p 〈 0.001). To understand the role of SWI/SNF mts in the context of driver co-mts, we compared the survival of D+ vs D- tumors for each SWI/SNF subunit. As expected, D+ tumors were associated with better survival in SWI/SNF wild-type (wt) tumors (HRs 0.76-0.78, p 〈 0.00001). There was no survival effect of ARID1A, ARID2 or PBRM1 mts (HRs = 0.9-1, p = ns). In contrast, in SMARCA4mts, D+ tumors had much worse survival than D- (HR = 1.295, p = 0.003). This effect is driven by the KRASmt cohort, as KRASmt/SMARCA4mt tumors had significantly worse survival compared with D- tumors (HR = 1.882, p 〈 0.001). Of note, KRASmts are enriched in the D+/SMARCA4mt subgroup (78% of all oncogenic drivers). When KRASmts were removed from the D+ group, no survival difference was observed between D+ and D- SMARCA4mt tumors (HR = 0.938, p = ns). Conclusions: In this largest-ever retrospective cohort of NSCLC patients with SWI/SNF mutations, SMARCA4mt is the only SWI/SNF alteration broadly associated with worse survival. SMARCA4mt is associated with particularly short survival in KRASmt tumors. These data suggest underlying biology which may inform further investigation and therapeutic development.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9039
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
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    Baseline peripheral T-cell composition in relation to radiographic phenotypes of immune-related pneumonitis.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 2545-2545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 2545-2545
    Abstract: 2545 Background: Pneumonitis is one of the most morbid complications from immune checkpoint inhibitor (ICI) treatment, but pathogenic mechanisms are unclear and no biomarkers permit pre-treatment risk assessment. We sought to characterize peripheral T cell subsets of pneumonitis patients on the single cell level. Methods: Blood was collected before and during ICI treatment in 24 patients. Cells were processed for single cell RNA sequencing (scRNAseq) employing CITEseq methodology using multiplexed cell surface markers labelled with a cocktail of oligonucleotide-tagged Total-Seq anti-human antibodies against CD4, CD8, CD45RA and CD27 followed by Chromium 10X sequencing. Principal Component Analysis was performed with iCellR, K-nearest-neighbor-based Network graph drawing Layout, and PhenoGraph clustering to assign cell types. CT scans were performed per standard of care and were reviewed by an experienced thoracic radiologist. Results: Seven of 24 patients developed pneumonitis; 9 did not experience an immune-related adverse event, and the remainder experienced arthritis (4), thyroiditis (3), or neurotoxicity (1). Pneumonitis patients had expanded proportions of TH2 TCF7 + T cells at baseline as compared to the other patients. Radiographically, two patients’ pneumonitis manifested as Chronic Hypersensitivity Pneumonitis (CHP), and four had Organized Pneumonia (OP). At baseline, CHP patients had significantly lower levels of CD8 + TCM cells (CXCR3+), double-positive T cells, gamma-delta T cells, and higher levels of naïve-like CD4 + TN TCF7 + LEF1 + and CD4 + TH1/2 CXCR3 + GATA3 + cells compared to OP. Gene expression levels also distinguished between these radiographic phenotypes. Conclusions: The peripheral T cell composition of patients who developed pneumonitis was distinct from those who did not in our cohort and unique by radiographic manifestation, suggesting potential pathogenic mechanisms and a prelude to circulating predictive markers of ICI toxicity.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.2545
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
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    Abstract 5902: Integrative genomic analysis of checkpoint blockade in lung cancer: A multi-institution SU2C collaborative
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5902-5902
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5902-5902
    Abstract: PD-1/PD-L1 checkpoint blockade has been a landmark advance for many patients suffering from advanced non-small cell lung cancer (NSCLC). However, detailed biomarkers of response beyond tumor mutational burden (TMB) are still poorly understood. As part of the effort to elucidate these additional signatures, we describe our progress on the Stand Up to Cancer Lung (SU2C-Lung) cohort. Initial characterization of exomes recapitulates mutational and copy number profiles seen in The Cancer Genome Atlas (TCGA) project. To better define expression subtypes using RNA sequencing, we performed non-negative matrix factorization (NMF) across an aggregated set of publicly available NSCLC expression data (including adenocarcinoma, squamous cell carcinoma, and large cell neuroendocrine histologies), and demonstrate good concordance in the SU2C-Lung cohort between this expression-based classifier and clinically annotated histology. To gain further insight into how immune cell infiltrates vary across our cohort, we additionally tested two common deconvolution algorithms, EPIC and CIBERSORT. While these two methods agree for some prominent cell types, such as B cells and CD4 T cells, discrepancies in minor infiltrating components such as NK cells may suggest a limit to the inference of rare subpopulations from bulk sequencing data.Finally, we describe a novel approach for determining single-gene predictors of response. Using the method, which is based on comparison of top single transcriptional features identified from random bootstraps of the full cohort as compared to a set of background shuffles, we are able to show that we remain powered for discovery of RNA response biomarkers despite the typically burdensome toll of multiple hypothesis correction at genome wide scale. Acknowledgment: Supported by Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant SU2C-AACR-DT17-15. Citation Format: Monica Arniella, Arvind Ravi, Chip Stewart, Sam Freeman, Mark Awad, Patrick Forde, Valsamo Anagnostou, Brian Henick, Jonathan Riess, Don Gibbons, Nathan Pennell, Vamsidhar Velcheti, Ignaty Leshchiner, Jaegil Kim, Subba Digumarthy, Mari Mino-Kenudson, John Heymach, Nir Hacohen, Naiyer Rizvi, Roy Herbst, Victor Velculescu, Julie Brahmer, Kurt Schalper, Pasi Jänne, Jedd Wolchok, Alice Shaw, Justin Gainor, Matthew Hellmann, Gad Getz. Integrative genomic analysis of checkpoint blockade in lung cancer: A multi-institution SU2C collaborative [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5902.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-5902
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 6
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    Elite Intratumoral T-cell Clonotypes (The 1%) Effect “Trickle-Down Cytotoxicity”
    American Association for Cancer Research (AACR) ; 2020
    In:  Clinical Cancer Research Vol. 26, No. 6 ( 2020-03-15), p. 1205-1207
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 6 ( 2020-03-15), p. 1205-1207
    Abstract: Careful study of T-cell clonal dynamics in patients with non–small cell lung cancer treated with neoadjuvant nivolumab suggests that successful trafficking of clones from a proliferative burst in the periphery to the tumor associates with major pathologic response. Integration of these findings with functional analysis may augment current therapeutic strategies. See related article by Zhang et al., p. 1327
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-19-3788
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 7
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    Abstract CT034: GLIMMER-01: initial results from a phase 1 dose escalation trial of a first-in-class bi-sialidase (E-602) in solid tumors
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 8_Supplement ( 2023-04-14), p. CT034-CT034
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 8_Supplement ( 2023-04-14), p. CT034-CT034
    Abstract: Background: Hypersialylation (excessive sialoglycans) on tumor cells has been known to be associated with poorer cancer outcomes for more than 40 years. Sialoglycans are immune suppressive and promote tumor immune evasion by binding to sialoglycan receptors (e.g. Siglecs) expressed on immune cells. However, redundant immune cell expression among Siglecs has posed a challenge for receptor-targeting therapeutic approaches. E-602 is a first-in-class fusion protein of engineered human sialidase (Neu2) and a human IgG1 Fc region. The dimeric sialidase moieties of E-602 circumvent the redundancy of this biology by directly cleaving terminal sialic acid residues from sialoglycans on immune and tumor cells. In preclinical studies, E-602 enhanced immune function by augmenting antigen-specific priming and activation of T cells and restoring function of exhausted-like T cells, and E-602 demonstrated antitumor activity as monotherapy in multiple mouse tumor models. Methods: A Phase 1/2 first-in-human dose escalation study is evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of E-602 in patients with advanced cancers. Eligible patients with select advanced solid tumors were treated with E-602 IV once weekly at dose levels between 1 and 30 mg/kg. Circulating immune cells were analyzed for changes in sialylation and immunophenotyping by flow cytometry. Changes in circulating cytokines were measured by immunoassays. Results: As of January 6, 2023, 32 patients were treated with at least one dose of E-602. The most common tumors treated were colorectal (n=18) and pancreatic (n=6). Doses up to 30 mg/kg were tolerated with no dose-limiting toxicities. The most frequent adverse event was infusion-related reactions which were primarily grade 1-2 and clinically manageable. PK was linear across the evaluated dose range with an estimated T1/2 of 9-24 hours. Dose dependent PD observations included (1) desialylation of peripheral CD8+ T, CD4+ T, and NK cells, remaining detectable in some patients at 7 days post-dose; (2) increases in the immune activation marker, CD69, on peripheral CD8+ T, CD4+ T, and NK cells; and (3) increases in the IFNγ-dependent chemokine CXCL10, TNF-α, and MIP1-β. Thus far, response-evaluable patients have had stable or progressive disease. Additional safety, PK, PD, and clinical outcomes for other patients treated as part of backfill at multiple dose levels will be reported at the meeting. Conclusion: E-602 is tolerated at doses up to 30 mg/kg. Consistent with preclinical findings, dose-dependent desialylation and immune system activation were observed. Based on the observed tolerability and PD effects, the Phase 2 portion of the study to evaluate clinical activity of E-602 monotherapy in patients with checkpoint-inhibitor resistant NSCLC and melanoma will proceed. Citation Format: Jason J. Luke, Melissa Johnson, Anthony Tolcher, Christopher T. Chen, Tong Dai, Brendan D. Curti, Anthony El-Khoueiry, Mario Sznol, Brian S. Henick, Christine Horak, Pushpa Jayaraman, Christopher B. Cole, Dawn Wilson, Lizhi Cao, Li Peng, David Feltquate, Deanne Lathers, Manish R. Sharma. GLIMMER-01: initial results from a phase 1 dose escalation trial of a first-in-class bi-sialidase (E-602) in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT034.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-CT034
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 8
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    Tumor-Derived CCL5 Recruits Cancer-Associated Fibroblasts and Promotes Tumor Cell Proliferation in Esophageal Squamous Cell Carcinoma
    American Association for Cancer Research (AACR) ; 2023
    In:  Molecular Cancer Research Vol. 21, No. 7 ( 2023-07-05), p. 741-752
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 7 ( 2023-07-05), p. 741-752
    Abstract: Cancer-associated fibroblasts (CAF) can promote tumor growth, metastasis, and therapeutic resistance in esophageal squamous cell carcinoma (ESCC), but the mechanisms of action remain elusive. Our objective was to identify secreted factor(s) that mediate the communication between CAFs and ESCC tumor cells with the aim of identifying potential druggable targets. Through unbiased cytokine arrays, we have identified CC motif chemokine ligand 5 (CCL5) as a secreted factor that is increased upon co-culture of ESCC cells and CAFs, which we replicated in esophageal adenocarcinoma (EAC) with CAFs. Loss of tumor-cell-derived CCL5 reduces ESCC cell proliferation in vitro and in vivo and we propose this is mediated, in part, by a reduction in ERK1/2 signaling. Loss of tumor-derived CCL5 reduces the percentage of CAFs recruited to xenograft tumors in vivo. CCL5 is a ligand for the CC motif receptor 5 (CCR5), for which a clinically approved inhibitor exists, namely Maraviroc. Maraviroc treatment reduced tumor volume, CAF recruitment, and ERK1/2 signaling in vivo, thus, mimicking the effects observed with genetic loss of CCL5. High CCL5 or CCR5 expression is associated with worse prognosis in low-grade esophageal carcinomas. Implications: These data highlight the role of CCL5 in tumorigenesis and the therapeutic potential of targeting the CCL5–CCR5 axis in ESCC.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1541-7786.MCR-22-0872
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 9
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    Abstract 5944: Relief of chromosomal instability-induced cGAS-STING signaling sensitizes STK11 -mutant non-small cell lung cancer to immune checkpoint blockade
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5944-5944
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5944-5944
    Abstract: Non-small cell lung cancers (NSCLCs) harboring deletions or inactivating mutations in STK11 (encoding LKB1) are associated with treatment-resistance, including to immune checkpoint blockade, and poor survival, yet the underlying mechanisms are poorly understood. Here, we combined multi-modal single-cell transcriptomics, whole-genome sequencing (WGS), and analysis of public data bases totaling & gt;10,000 NSCLC whole-exome sequencing (WES) and when available RNA (RNA-seq) profiles of AACR GENIE, MSK IMPACT, TCGA and CPTAC, high-content imaging, and functional assays, to determine genomic and mechanistic features of STK11-mutant NSCLC. Across human WES/RNA-seq data, we find that STK11-mutant NSCLC have a significantly higher fraction of genome altered (FGA) and score strongly for the mRNA-based CIN70 signature compared to other NSCLC genotypes, overall indicating that these tumors have a higher degree of chromosomal instability (CIN). Using high-content imaging, we show that both human and murine STK11-mutant models have a higher rate of micronuclei and chromosome-mis-segregation events, confirming their CINhigh status in dynamic assays. Next, we show that tonic CIN-induced activation of cGAS-STING signaling, whose activation is typically thought of inducing type I interferon expression, results in strong suppression of anti-tumor immune signaling. Remarkably, genetic or pharmacologic suppression of cGAS, and thus depletion of the STING ligand cGAMP, results in reprogramming and re-sensitization of STK11-mutant models to cGAS-STING mediated type I interferon responses. Furthermore, we show that CIN promotes excessive production cGAMP in STK11-mutant models. We find upregulation of two ectonucleotidases (ENPP1 and CD73/NT5E) that hydrolyze exported cGAMP to adenosine, which may further contribute to the highly dysfunctional tumor-microenvironment observed in STK11-mutant tumors. Lastly, suppression of CIN through overexpression of mitotic-centromere associated kinesin (MCAK) in murine STK11-mutant models results in decreased tumor growth and sensitization to anti-PD1 therapy. In summary, we define STK11-mutant as archetypical chromosomally form of NSCLC, provide mechanistic basis that corelates with poor clinical outcomes, and demonstrate how relief of tonic CIN-induced changes may be therapeutically leveraged. Citation Format: Lindsay A. Caprio, Christy Hong, Amit Dipak Amin, Somnath Tagore, Johannes Melms, Luke Cai, Yiping Wang, Patricia Ho, Michael Mu, Hanina Hibshoosh, Brian Henick, Kwok K. Wong, Samuel F. Bakhoum, Benjamin Izar. Relief of chromosomal instability-induced cGAS-STING signaling sensitizes STK11-mutant non-small cell lung cancer to immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5944.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-5944
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 10
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    Abstract 2674: Immune profiling of in NSCLC shows expression of PD-L1 in macrophages is better associated with outcomes than PD-L1 in tumor cells in PD-1 axis immunotherapy treated patients
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2674-2674
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2674-2674
    Abstract: Background: The immune checkpoint target and companion diagnostic, PD-L1 is expressed in both tumor cell and immune cells and both are read by the pathologist and associated with response to therapy in different organ systems. Here, we examine the expression of PD-L1 using molecular assessment of cellular localization to determine which cell type carries the predictive value of the companion diagnostic test. Methods: We used the quantitative immunofluorescence (QIF) methods (AQUA analysis of images from the PM2000 and inForm analysis of images from the PerkinElmer Vectra and Polaris Automated Quantitative Pathology Imaging System) and measured the expression of PD-L1 in multiple immune cell types by phenotyping each cell. We also acquired high resolution images from the multiplex for precise identification of co-localization using confocal microscopy. The PD-L1 localization was measured using two multiplex QIF panels including CD56 for natural killer (NK) cells, CD68 for macrophages and CD8 for cytotoxic T cells. This multiplex was performed on three retrospective Yale NSCLC cohorts (457 non-immunotherapy-treated cases and 62 PD-1 axis immunotherapy treated cases) represented in tissue microarrays. Results: PD-L1 localization was significantly higher in macrophages compared to NK cells and CD8 T cells in both tumor and stroma compartment. In stroma, 80% of PD-L1 is expressed by macrophages, while 5% and 3% by NK cells and CD8 T cells, respectively. High CD8 level (top tertile) was associated with better overall survival (P & lt;0.05) predominantly driven by the stroma CD8 (P & lt;0.05), independent of sex, stage, smoking status, and age. Elevated PD-L1 in macrophages was associated with high PD-L1 level in tumor as well as CD8 level and CD68 level (P & lt;0.05). High PD-L1 expression in CD68+ macrophages was correlated better overall survival (OS; P = .0448) while high PD-L1 expression in tumor cells was not. Conclusion: In over 500 lung cancer cases the predominant immune cell type that expresses PD-L1 CD68 positive macrophages, as compared to NK cells and CD8 T cells. The level of PD-L1 in macrophages is significantly associated with the level of PD-L1 in tumor and with high levels of CD8+ T cells, suggesting a connection between high PD-L1 and “hot” tumors. Similar to our previous findings in melanoma, we find that high levels of PD-L1 in macrophages is a positive predictive biomarker for PD-1 pathway blockade therapy. Due to the small size of the treated cohort in the study, further work is required to confirm this observation. Citation Format: Yuting Liu, Jon Zugazagoitia, Brian Henick, Kurt A. Schalper, David L. Rimm. Immune profiling of in NSCLC shows expression of PD-L1 in macrophages is better associated with outcomes than PD-L1 in tumor cells in PD-1 axis immunotherapy treated patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2674.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-2674
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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