LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: Longitudinal Immune Profiling Reveals Unique Myeloid and T-cell Phenotypes Associated with Spontaneous Immunoediting in a Prostate Tumor Model.

    Ager, Casey R / Obradovic, Aleksandar Z / Arriaga, Juan M / Chaimowitz, Matthew G / Califano, Andrea / Abate-Shen, Cory / Drake, Charles G

    Cancer immunology research

    2021  Volume 9, Issue 5, Page(s) 529–541

    Abstract: The theory of cancer immunoediting, which describes the dynamic interactions between tumors and host immune cells that shape the character of each compartment, is foundational for understanding cancer immunotherapy. Few models exist that facilitate in- ... ...

    Abstract The theory of cancer immunoediting, which describes the dynamic interactions between tumors and host immune cells that shape the character of each compartment, is foundational for understanding cancer immunotherapy. Few models exist that facilitate in-depth study of each of the three canonical phases of immunoediting: elimination, equilibrium, and escape. Here, we utilized NPK-C1, a transplantable prostate tumor model that we found recapitulated the three phases of immunoediting spontaneously in immunocompetent animals. Given that a significant portion of NPK-C1 tumors reliably progressed to the escape phase, we were able to delineate cell types and mechanisms differentially prevalent in equilibrium versus escape phases. Using high-dimensional flow cytometry, we found that activated CD4
    MeSH term(s) Animals ; Antigens, CD/immunology ; CD8-Positive T-Lymphocytes/immunology ; Disease Models, Animal ; Flow Cytometry ; Integrin alpha Chains/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Phenotype ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/pathology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/immunology ; Tumor Burden/immunology ; Tumor Escape ; Tumor Microenvironment/immunology
    Chemical Substances Antigens, CD ; Integrin alpha Chains ; alpha E integrins
    Language English
    Publishing date 2021-02-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-20-0637
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 7022: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma.

    Singla, Nirmish / Nirschl, Thomas R / Obradovic, Aleksandar Z / Shenderov, Eugene / Lombardo, Kara / Liu, Xiaopu / Pons, Alice / Zarif, Jelani C / Rowe, Steven P / Trock, Bruce J / Hammers, Hans J / Bivalacqua, Trinity J / Pierorazio, Phillip M / Deutsch, Julie S / Lotan, Tamara L / Taube, Janis M / Ged, Yasser M A / Gorin, Michael A / Allaf, Mohamad E /
    Drake, Charles G

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 1458

    Abstract: Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to ... ...

    Abstract Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
    MeSH term(s) Humans ; Nivolumab/pharmacology ; Carcinoma, Renal Cell/drug therapy ; Kidney Neoplasms ; Neoadjuvant Therapy ; Prospective Studies
    Chemical Substances Nivolumab (31YO63LBSN)
    Language English
    Publishing date 2024-01-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-51889-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death.

    Choe, Joshua H / Kawase, Tatsuya / Xu, An / Guzman, Asja / Obradovic, Aleksandar Z / Low-Calle, Ana Maria / Alaghebandan, Bita / Raghavan, Ananya / Long, Kaitlin / Hwang, Paul M / Schiffman, Joshua D / Zhu, Yan / Zhao, Ruiying / Lee, Dung-Fang / Katz, Chen / Prives, Carol

    Cancer discovery

    2023  Volume 13, Issue 5, Page(s) 1250–1273

    Abstract: Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer- ... ...

    Abstract Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li-Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein. Further, p53(A347D) cannot bind or transactivate the majority of canonical p53 target genes. Isogenic cell lines harboring either p53(A347D) or no p53 yield comparable tumorigenic properties, yet p53(A347D) displays remarkable neomorphic activities. Cells bearing p53(A347D) possess a distinct transcriptional profile and undergo metabolic reprogramming. Further, p53(A347D) induces striking mitochondrial network aberration and associates with mitochondria to drive apoptotic cell death upon topoisomerase II inhibition in the absence of transcription. Thus, dimer-forming p53 demonstrates both loss-of-function (LOF) and gain-of-function (GOF) properties compared with the wild-type form of the protein.
    Significance: A mutant p53 (A347D), which can only form dimers, is associated with increased cancer susceptibility in LFS individuals. We found that this mutant wields a double-edged sword, driving tumorigenesis through LOF while gaining enhanced apoptogenic activity as a new GOF, thereby yielding a potential vulnerability to select therapeutic approaches. See related commentary by Stieg et al., p. 1046. See related article by Gencel-Augusto et al., p. 1230. This article is highlighted in the In This Issue feature, p. 1027.
    MeSH term(s) Humans ; Li-Fraumeni Syndrome/genetics ; Li-Fraumeni Syndrome/metabolism ; Li-Fraumeni Syndrome/pathology ; Transcriptional Activation ; Tumor Suppressor Protein p53/metabolism ; Apoptosis/genetics ; Mitochondria/metabolism
    Chemical Substances Tumor Suppressor Protein p53
    Language English
    Publishing date 2023-04-11
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-22-0882
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6916: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.

    Hawley, Jessica E / Obradovic, Aleksandar Z / Dallos, Matthew C / Lim, Emerson A / Runcie, Karie / Ager, Casey R / McKiernan, James / Anderson, Christopher B / Decastro, Guarionex J / Weintraub, Joshua / Virk, Renu / Lowy, Israel / Hu, Jianhua / Chaimowitz, Matthew G / Guo, Xinzheng V / Zhang, Ya / Haffner, Michael C / Worley, Jeremy / Stein, Mark N /
    Califano, Andrea / Drake, Charles G

    Cancer cell

    2023  Volume 41, Issue 11, Page(s) 1972–1988.e5

    Abstract: When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in ... ...

    Abstract When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients.
    MeSH term(s) Male ; Humans ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Androgen Antagonists/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Androgens/therapeutic use ; Immunotherapy ; Castration ; Tumor Microenvironment
    Chemical Substances Androgen Antagonists ; Androgens
    Language English
    Publishing date 2023-11-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2023.10.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5650: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 104: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Blocking IL1 Beta Promotes Tumor Regression and Remodeling of the Myeloid Compartment in a Renal Cell Carcinoma Model: Multidimensional Analyses.

    Aggen, David H / Ager, Casey R / Obradovic, Aleksandar Z / Chowdhury, Nivedita / Ghasemzadeh, Ali / Mao, Wendy / Chaimowitz, Matthew G / Lopez-Bujanda, Zoila A / Spina, Catherine S / Hawley, Jessica E / Dallos, Matthew C / Zhang, Cheng / Wang, Vinson / Li, Hu / Guo, Xinzheng V / Drake, Charles G

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 27, Issue 2, Page(s) 608–621

    Abstract: Purpose: Intratumoral immunosuppression mediated by myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) represents a potential mechanism of immune checkpoint inhibitor (ICI) resistance in solid tumors. By promoting TAM and ... ...

    Abstract Purpose: Intratumoral immunosuppression mediated by myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) represents a potential mechanism of immune checkpoint inhibitor (ICI) resistance in solid tumors. By promoting TAM and MDSC infiltration, IL1β may drive adaptive and innate immune resistance in renal cell carcinoma (RCC) and in other tumor types.
    Experimental design: Using the RENCA model of RCC, we evaluated clinically relevant combinations of anti-IL1β plus either anti-PD-1 or the multitargeted tyrosine kinase inhibitor (TKI), cabozantinib. We performed comprehensive immune profiling of established RENCA tumors via multiparameter flow cytometry, tumor cytokine profiling, and single-cell RNA sequencing (RNA-seq). Similar analyses were extended to the MC38 tumor model.
    Results: Analyses via multiparameter flow cytometry, tumor cytokine profiling, and single-cell RNA-seq showed that anti-IL1β reduces infiltration of polymorphonuclear MDSCs and TAMs. Combination treatment with anti-IL1β plus anti-PD-1 or cabozantinib showed increased antitumor activity that was associated with decreases in immunosuppressive MDSCs and increases in M1-like TAMs.
    Conclusions: Single-cell RNA-seq analyses show that IL1β blockade and ICI or TKI remodel the myeloid compartment through nonredundant, relatively T-cell-independent mechanisms. IL1β is an upstream mediator of adaptive myeloid resistance and represents a potential target for kidney cancer immunotherapy.
    MeSH term(s) Anilides/administration & dosage ; Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism ; Cell Line, Tumor ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; Mice ; Mice, Inbred BALB C ; Myeloid-Derived Suppressor Cells/drug effects ; Myeloid-Derived Suppressor Cells/metabolism ; Pyridines/administration & dosage ; RNA-Seq/methods ; Single-Cell Analysis/methods ; Treatment Outcome ; Tumor Burden/drug effects ; Tumor Burden/genetics ; Tumor-Associated Macrophages/classification ; Tumor-Associated Macrophages/drug effects ; Tumor-Associated Macrophages/metabolism
    Chemical Substances Anilides ; Cytokines ; Immune Checkpoint Inhibitors ; Interleukin-1beta ; Pyridines ; cabozantinib (1C39JW444G)
    Language English
    Publishing date 2020-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-1610
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer.

    Obradovic, Aleksandar Z / Dallos, Matthew C / Zahurak, Marianna L / Partin, Alan W / Schaeffer, Edward M / Ross, Ashley E / Allaf, Mohamad E / Nirschl, Thomas R / Liu, David / Chapman, Carolyn G / O'Neal, Tanya / Cao, Haiyi / Durham, Jennifer N / Guner, Gunes / Baena-Del Valle, Javier A / Ertunc, Onur / De Marzo, Angelo M / Antonarakis, Emmanuel S / Drake, Charles G

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 13, Page(s) 3182–3192

    Abstract: Purpose: Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown.: Patients and methods: We conducted a neoadjuvant, ... ...

    Abstract Purpose: Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown.
    Patients and methods: We conducted a neoadjuvant, randomized study to quantify the immunologic effects of a GM-CSF-secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy.
    Results: Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8
    Conclusions: Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8
    MeSH term(s) Aged ; Androgen Antagonists/pharmacology ; Androgen Antagonists/therapeutic use ; Biomarkers, Tumor ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/adverse effects ; Cancer Vaccines/therapeutic use ; Combined Modality Therapy ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Lymphocytes, Tumor-Infiltrating/pathology ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/mortality ; Prostatic Neoplasms/therapy ; Recurrence ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/pathology ; Treatment Outcome ; Tumor Microenvironment/immunology ; Vaccination
    Chemical Substances Androgen Antagonists ; Biomarkers, Tumor ; Cancer Vaccines
    Language English
    Publishing date 2020-03-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-19-3372
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top