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  1. Article ; Online: Immune-Pathogenesis of Myeloma.

    Dhodapkar, Madhav V

    Hematology/oncology clinics of North America

    2024  Volume 38, Issue 2, Page(s) 281–291

    Abstract: This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing immune dysfunction and spatial immune exclusion. As the conditions progress, a shift ... ...

    Abstract This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing immune dysfunction and spatial immune exclusion. As the conditions progress, a shift toward myeloma involves ongoing immune impairment, affecting both innate and adaptive immunity. Intriguingly, even in advanced myeloma stages, susceptibility to immune effector cells persists. This insight highlights the intricate interplay between immune responses and the development of these conditions, paving the way for potential therapeutic interventions targeting immune modulation in the management of MGUS and myeloma.
    MeSH term(s) Humans ; Multiple Myeloma/etiology ; Multiple Myeloma/therapy ; Monoclonal Gammopathy of Undetermined Significance/etiology ; Monoclonal Gammopathy of Undetermined Significance/therapy ; Disease Progression
    Language English
    Publishing date 2024-01-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 93115-9
    ISSN 1558-1977 ; 0889-8588
    ISSN (online) 1558-1977
    ISSN 0889-8588
    DOI 10.1016/j.hoc.2023.12.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Role of Natural Killer T (NKT) Cells in Myeloma Biology and Therapy.

    Dhodapkar, Madhav V

    Critical reviews in oncogenesis

    2024  Volume 29, Issue 1, Page(s) 63–68

    Abstract: Natural Killer T (NKT) cells are distinct innate lymphocytes that recognize lipid antigens in the context of nonpolymorphic molecule CD1d. Multiple myeloma (MM) is a hematologic malignancy wherein malignant plasma cells express CD1d and are sensitive to ... ...

    Abstract Natural Killer T (NKT) cells are distinct innate lymphocytes that recognize lipid antigens in the context of nonpolymorphic molecule CD1d. Multiple myeloma (MM) is a hematologic malignancy wherein malignant plasma cells express CD1d and are sensitive to lysis by NKT cells. Progressive malignancy in MM is characterized by NKT cell dysfunction. Several studies have tried to harness the anti-tumor properties of NKT cells in MM to mediate tumor regression. NKT cells are also attractive targets for approaches at immune redirection in MM with chimeric-antigen receptor NKT (CAR-NKT) and bispecific antibodies. In addition to the commonly studied invariant-NKT (iNKT) cells, MM patients often also exhibit alterations in type-II NKT cells and their ligands. In patients and mouse models with Gaucher disease (GD), an inherited lipid-storage disorder with markedly increased risk for MM, distinct type-II NKT cells exhibit a T-follicular helper (NKT-TFH) phenotype and provide help to lipid-specific B cells. Chronic immune activation in this setting eventually sets the stage for malignancy, which can be targeted in both mouse models and GD patients by reducing the underlying antigen. NKT cells are thus integrally linked to MM pathogenesis and an attractive target for MM immunotherapy.
    MeSH term(s) Animals ; Mice ; Humans ; Multiple Myeloma/therapy ; Natural Killer T-Cells ; Disease Models, Animal ; Killer Cells, Natural ; Biology ; Lipids
    Chemical Substances Lipids
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1036388-9
    ISSN 0893-9675
    ISSN 0893-9675
    DOI 10.1615/CritRevOncog.2023048380
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2587: Show issues Location:
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  3. Article ; Online: Immune status and selection of patients for immunotherapy in myeloma: a Proposal.

    Dhodapkar, Madhav V

    Blood advances

    2024  

    Abstract: Newer immune-based approaches based on recruitment and redirection of endogenous and/or synthetic immunity such as chimeric antigen-receptor-T (CAR-T) cells or bispecific antibodies are transforming the clinical management of multiple myeloma (MM). ... ...

    Abstract Newer immune-based approaches based on recruitment and redirection of endogenous and/or synthetic immunity such as chimeric antigen-receptor-T (CAR-T) cells or bispecific antibodies are transforming the clinical management of multiple myeloma (MM). Contributions of the immune system to the anti-tumor effects of myeloma therapies are also increasingly appreciated. Clinical malignancy in MM originates in the setting of systemic immune alterations that begin early in myelomagenesis and regional changes in immunity impacted by spatial contexture. Pre-existing and therapy-induced changes in immune cells correlate with outcomes in MM patients including following immune therapies. Here we discuss insights from and limitation of current data about immune status and outcomes following immune therapies in MM patients. Pre-existing variation in systemic and/or regional immunity is emerging as a major determinant of the efficacy of current immune therapies as well as vaccines. MM is however a multifocal malignancy. As with solid tumors, integrating spatial aspects of the tumor and consideration of immune targets with biology of immune cells may be critical to optimize the application of immune therapy including T cell redirection in MM. We propose 5 distinct spatial immune types of MM- immune-depleted, immune-permissive, immune-excluded, immune-suppressed, and immune-resistant, that may provide an initial framework for optimal application of specific immune therapies in MM. Such considerations may also help optimize rational patient selection for emerging immune therapies to improve outcomes.
    Language English
    Publishing date 2024-04-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023011242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Harnessing Dendritic Cells: Next Frontier for Durable Immune Control in Myeloma.

    Dhodapkar, Madhav V

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

    2023  Volume 29, Issue 22, Page(s) 4524–4526

    Abstract: Immune-based approaches including T-cell redirection have transformed the therapeutic landscape in myeloma. Injection of dendritic cells (DC) led to the induction of immune responses in vaccinated patients with myeloma. These studies pave the way for ... ...

    Abstract Immune-based approaches including T-cell redirection have transformed the therapeutic landscape in myeloma. Injection of dendritic cells (DC) led to the induction of immune responses in vaccinated patients with myeloma. These studies pave the way for future combination strategies harnessing DCs to enhance tumor immunity and improve outcomes in myeloma. See related article by Freeman et al., p. 4575.
    MeSH term(s) Humans ; Multiple Myeloma/pathology ; Dendritic Cells ; T-Lymphocytes ; Cancer Vaccines/therapeutic use
    Chemical Substances Cancer Vaccines
    Language English
    Publishing date 2023-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-2292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4223: Show issues Location:
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  5. Article ; Online: The immune system in multiple myeloma and precursor states: Lessons and implications for immunotherapy and interception.

    Dhodapkar, Madhav V

    American journal of hematology

    2022  Volume 98 Suppl 2, Page(s) S4–S12

    Abstract: Multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) are distinct disorders that likely originate in the setting of chronic immune activation. Evolution of these lesions is impacted by cross-talk with both ... ...

    Abstract Multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) are distinct disorders that likely originate in the setting of chronic immune activation. Evolution of these lesions is impacted by cross-talk with both innate and adaptive immune systems of the host. Harnessing the immune system may, therefore, be an attractive strategy to prevent clinical malignancy. While clinical MM is characterized by both regional and systemic immune suppression and paresis, immune-based approaches, particularly redirecting T cells have shown remarkable efficacy in MM patients. Optimal application and sequencing of these new immune therapies and their integration into clinical MM management may depend on the underlying immune status, in turn impacted by host, tumor, and environmental features. Immune therapies carry the potential to achieve durable unmaintained responses and cures in MM.
    MeSH term(s) Humans ; Multiple Myeloma/pathology ; Monoclonal Gammopathy of Undetermined Significance/therapy ; Monoclonal Gammopathy of Undetermined Significance/pathology ; T-Lymphocytes/pathology ; Immunotherapy
    Language English
    Publishing date 2022-10-24
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26752
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1251: Show issues Location:
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  6. Article ; Online: It takes T to tango: immunotherapy in MM.

    Gupta, Vikas A / Dhodapkar, Madhav V

    Blood

    2022  Volume 139, Issue 9, Page(s) 1259–1260

    MeSH term(s) Immunologic Factors ; Immunotherapy
    Chemical Substances Immunologic Factors
    Language English
    Publishing date 2022-03-03
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021013816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Role of B cells in immune-related adverse events following checkpoint blockade.

    Dhodapkar, Kavita M / Duffy, Alyssa / Dhodapkar, Madhav V

    Immunological reviews

    2023  Volume 318, Issue 1, Page(s) 89–95

    Abstract: Blockade of immune checkpoints has transformed the therapy of several cancers. However, immune-related adverse events (irAEs) have emerged as a major challenge limiting the clinical application of this approach. B cells are recognized as major players in ...

    Abstract Blockade of immune checkpoints has transformed the therapy of several cancers. However, immune-related adverse events (irAEs) have emerged as a major challenge limiting the clinical application of this approach. B cells are recognized as major players in the pathogenesis of human autoimmunity and have been successfully targeted to treat these disorders. While T cells have been extensively studied as therapeutic targets of immune checkpoint blockade (ICB), these checkpoints also impact B cell tolerance. Blockade of immune checkpoints in the clinic is associated with distinct changes in the B cell compartment that correlate with the development of irAEs. In this review, we focus on the possible role of humoral immunity, specifically human B cell subsets and autoantibodies in the pathogenesis of ICB-induced irAEs. There remains an unmet need to better understand the T:B cell cross talk underlying the activation of pathogenic B cells and the development of ICB-induced irAEs. Such studies may identify new targets or approaches to prevent or treat irAEs and improve the application of ICB therapy in cancer.
    MeSH term(s) Humans ; Neoplasms/drug therapy ; B-Lymphocytes/pathology ; Autoimmunity ; Immune Checkpoint Inhibitors/adverse effects ; Autoantibodies ; Immunotherapy/adverse effects
    Chemical Substances Immune Checkpoint Inhibitors ; Autoantibodies
    Language English
    Publishing date 2023-07-08
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13238
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book: Immunotherapy of cancer

    Dhodapkar, Madhav V.

    (Hematology oncology clincis of North America ; 20,3)

    2006  

    Author's details guest ed. Madhav V. Dhodapkar
    Series title Hematology oncology clincis of North America ; 20,3
    Hematology, oncology clinics of North America
    Collection Hematology, oncology clinics of North America
    Keywords Krebs ; Immuntherapie
    Subject Immunotherapie ; Carcinom ; Malignom ; Maligner Tumor ; Neoplasma ; Karzinom ; Bösartiger Tumor ; Krebserkrankung
    Language English
    Size XII S., S. 567 - 771 : Ill.
    Publisher Saunders
    Publishing place Philadelphia u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT014805289
    ISBN 1-4160-3905-8 ; 978-1-4160-3905-1
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Se 1077 -20,3- verfügbar in Königswinter Königswinter

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  9. Article ; Online: Role of B cells in immune‐related adverse events following checkpoint blockade

    Dhodapkar, Kavita M. / Duffy, Alyssa / Dhodapkar, Madhav V.

    Immunological Reviews. 2023 Sept., v. 318, no. 1 p.89-95

    2023  

    Abstract: Blockade of immune checkpoints has transformed the therapy of several cancers. However, immune‐related adverse events (irAEs) have emerged as a major challenge limiting the clinical application of this approach. B cells are recognized as major players in ...

    Abstract Blockade of immune checkpoints has transformed the therapy of several cancers. However, immune‐related adverse events (irAEs) have emerged as a major challenge limiting the clinical application of this approach. B cells are recognized as major players in the pathogenesis of human autoimmunity and have been successfully targeted to treat these disorders. While T cells have been extensively studied as therapeutic targets of immune checkpoint blockade (ICB), these checkpoints also impact B cell tolerance. Blockade of immune checkpoints in the clinic is associated with distinct changes in the B cell compartment that correlate with the development of irAEs. In this review, we focus on the possible role of humoral immunity, specifically human B cell subsets and autoantibodies in the pathogenesis of ICB‐induced irAEs. There remains an unmet need to better understand the T:B cell cross talk underlying the activation of pathogenic B cells and the development of ICB‐induced irAEs. Such studies may identify new targets or approaches to prevent or treat irAEs and improve the application of ICB therapy in cancer.
    Keywords B-lymphocytes ; autoantibodies ; autoimmunity ; humans ; humoral immunity ; pathogenesis ; therapeutics
    Language English
    Dates of publication 2023-09
    Size p. 89-95.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note REVIEW
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13238
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Navigating the Fas lane to improved cellular therapy for cancer.

    Dhodapkar, Madhav V

    The Journal of clinical investigation

    2019  Volume 129, Issue 4, Page(s) 1522–1523

    Abstract: Genetically engineered T cells have shown promising activity in the treatment of cancer. However, these cells are also potentially susceptible to immune-suppressive pathways in the tumor microenvironment that may limit their efficacy. In this issue of ... ...

    Abstract Genetically engineered T cells have shown promising activity in the treatment of cancer. However, these cells are also potentially susceptible to immune-suppressive pathways in the tumor microenvironment that may limit their efficacy. In this issue of the JCI, Yamamoto et al. describe a new cellular engineering approach to prevent Fas-mediated inhibition of T cell function, which may be exploited to improve cellular therapy for cancer.
    MeSH term(s) Humans ; Immunotherapy, Adoptive ; Neoplasms ; Signal Transduction ; T-Lymphocytes ; Tumor Microenvironment
    Language English
    Publishing date 2019-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI127581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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