GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (5)
  • 1
    Online Resource
    Online Resource
    Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Discovery Vol. 7, No. 7 ( 2017-07-01), p. 716-735
    Details
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 7, No. 7 ( 2017-07-01), p. 716-735
    Abstract: Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSC). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML cells are enriched in neither immature, quiescent cells nor LSCs. Strikingly, AraC-resistant preexisting and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status. AraC residual cells exhibited increased fatty-acid oxidation, upregulated CD36 expression, and a high OXPHOS gene signature predictive for treatment response in PDX and patients with AML. High OXPHOS but not low OXPHOS human AML cell lines were chemoresistant in vivo. Targeting mitochondrial protein synthesis, electron transfer, or fatty-acid oxidation induced an energetic shift toward low OXPHOS and markedly enhanced antileukemic effects of AraC. Together, this study demonstrates that essential mitochondrial functions contribute to AraC resistance in AML and are a robust hallmark of AraC sensitivity and a promising therapeutic avenue to treat AML residual disease. Significance: AraC-resistant AML cells exhibit metabolic features and gene signatures consistent with a high OXPHOS status. In these cells, targeting mitochondrial metabolism through the CD36–FAO–OXPHOS axis induces an energetic shift toward low OXPHOS and strongly enhanced antileukemic effects of AraC, offering a promising avenue to design new therapeutic strategies and fight AraC resistance in AML. Cancer Discov; 7(7); 716–35. ©2017 AACR. See related commentary by Schimmer, p. 670. This article is highlighted in the In This Issue feature, p. 653
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    URL: Article
    DOI: 10.1158/2159-8290.CD-16-0441
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2607892-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 66: BCG can subvert patients antitumor immune response by downregulating HLA-I expression on cancer cells
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 66-66
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 66-66
    Abstract: Patients with high-risk non muscle-invasive bladder cancer (NMIBC) frequently relapse after standard BCG immunotherapy and have a dismal outcome after progression to muscle-invasive bladder cancer (MIBC). The mechanisms of tumor resistance to such immunotherapy remain elusive. We performed functional assays of fresh bladder tumors mixed with BCG, reinforced with in vitro experiments and in situ immune profiling of a cohort of MIBC pre- and post BCG therapy. Here, we demonstrate two distinct patterns of BCG-induced immune subversion. In the first pattern, intracellular BCG infection was associated with HLA-I loss and epithelial-to- mesenchymal transition (EMT) characteristics. HLA-I deficient tumors displayed a myeloid immunosuppressive microenvironment and dismal outcomes. Conversely, HLA-I+ BCG-treated tumors generated a Th1 type of immune response associated with an upregulation of exhaustion markers. Such patients had a very favorable outcome upon radical surgery. We surmise that HLA-I expression in bladder cancers does not result from immunoediting but rather from a BCG-induced EMT process that predicts dismal prognosis. Cancer cells HLA-I scoring by immunohistochemistry (IHC) staining can be easily implemented by pathologists in routine practice in order to stratify future urothelial cancer patient treatment strategies. Citation Format: Mathieu Rouanne, Julien Adam, Camélia Radulescu, Séverine Mouraud, Delphine Bredel, Diane Letourneur, Tuan Zea Tan, Nicolas Signolle, Amélie Bigorgne, Michael Dussiot, Sandrine Susini, Lambros Tselikas, François-Xavier Danlos, Roman Chabanon, Anna K. Schneider, Sophie Vacher, Thierry Lebret, Ivan Bièche, Yves Allory, Jean-Charles Soria, Jean Paul Thiery, Laurence Zitvogel, Aurélien Marabelle. BCG can subvert patients antitumor immune response by downregulating HLA-I expression on cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 66.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-66
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Discovery Vol. 13, No. 4 ( 2023-04-03), p. 858-879
    Details
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 13, No. 4 ( 2023-04-03), p. 858-879
    Abstract: Cancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas’ primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti–PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology. Significance: Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti–PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies. This article is highlighted in the In This Issue feature, p. 799
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    URL: Article
    DOI: 10.1158/2159-8290.CD-22-0886
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2607892-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 3112: Prospective immune phenotyping of neuroblastoma children at diagnosis reveals specific immune defects related to the aggressiveness of the disease
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3112-3112
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3112-3112
    Abstract: CONTEXT: Neuroblastoma is the most common extracranial solid tumor in children. Patients with low- and intermediate-risk neuroblastoma (LIRNB) have favorable prognosis and an excellent five-year survival rate of more than 90%. However, in the case of high-risk neuroblastoma (HRNB; ~50% of cases), the prognosis of treatment remains unfavorable and the five-year survival rate remains under 40% despite aggressive multi modal therapy. QUESTION: We wanted to know if there was a defect in immune surveillance that could explain part of the aggressive phenotype of HRNB. METHODS: We performed a prospective multi-center study on thirty two new cases of neuroblastoma at all stages. We performed a wide phenotyping of immune cells by flow cytometry in fresh whole blood, and fresh whole bone marrow at diagnosis of children diagnosed for neuroblastoma. Cell counts were performed in order to be able to reason in absolute values (G/L) rather than only percentages. RESULTS: Blood and bone marrow from 20 LIRNB and 12 HRNB were prospectively analyzed. We found that specific subsets of circulating immune cells such as myeloid dendritic cells BDCA-1+, plasmacytoid dendritic cells, Teff/Treg CD4+ T-cells, were decreased in HRNB blood compared to LIRNB groups as opposed to other subsets (e.g iNKT, g9d2 T-cells,⋯). More surprisingly, these differences were not due to defects in cell production as there was no difference found for the same cell populations in the bone marrow between LIRNB and HRNB children. CONCLUSION: Specific immune cell defects are found in the blood from High risk neuroblastoma children that are not present in the blood of low & intermediate risk neuroblastoma children. These defects are not due to bone marrow production impairment. These results suggest that high risk neuroblastoma disease generates an impairment in the immune homeostasis of children. Gene expression analysis of cytokine/chemokine from these neuroblastoma tumors is underway (NCT01295762). Citation Format: Sandrine Susini, Isabelle Rochet, Estelle Verronèse, Christine Bardin, Chantal Rigal, Cécile Conter, Perrine Marec-Bérard, Christophe Bergeron, Audrey Lardy-Cleaud, Séverine Neymarc, Séverine Metzger, Jean-Louis Stephan, Dominique Plantaz, Christophe Caux, Christine Ménétrier-Caux, Aurelien Marabelle. Prospective immune phenotyping of neuroblastoma children at diagnosis reveals specific immune defects related to the aggressiveness of the disease [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):Abstra ct nr 3112.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-3112
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Interventional Radiology for Local Immunotherapy in Oncology
    American Association for Cancer Research (AACR) ; 2021
    In:  Clinical Cancer Research Vol. 27, No. 10 ( 2021-05-15), p. 2698-2705
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 10 ( 2021-05-15), p. 2698-2705
    Abstract: Human intratumoral immunotherapy (HIT-IT) is under rapid development, with promising preliminary results and high expectations for current phase III trials. While outcomes remain paramount for patients and the referring oncologists, the technical aspects of drug injection are critical to the interventional radiologist to ensure optimal and reproducible outcomes. The technical considerations for HIT-IT affect the safety, efficacy, and further development of this treatment option. Image-guided access to the tumor allows the therapeutic index of a treatment to be enhanced by increasing the intratumoral drug concentration while minimizing its systemic exposure and associated on-target off-tumor adverse events. Direct access to the tumor also enables the acquisition of cancer tissue for sequential sampling to better understand the pharmacodynamics of the injected immunotherapy and its efficacy through correlation of immune responses, pathologic responses, and imaging tumor response. The aim of this article is to share the technical insights of HIT-IT, with particular consideration for patient selection, lesion assessment, image guidance, and technical injection options. In addition, the organization of a standard patient workflow is discussed, so as to optimize HIT-IT outcome and the patient experience.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-19-4073
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...