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Research papers on Cancer immunotherapy

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  1. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group

    I. Puzanov, A. Diab, K. Abdallah, et al. · 2017 · Journal for Immunotherapy of Cancer · 1,808 citations

    Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs’ therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less f

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  2. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs

    Alyson Haslam, Vinay K. Prasad · 2019 · JAMA Network Open · 1,408 citations

    Importance: Immunotherapy checkpoint inhibitors have generated considerable interest because of durable responses in a number of hitherto intractable tumor types. Objective: To estimate the percentage of patients with cancer in the United States who are eligible for and respond to checkpoint inhibitor drugs approved for oncology indications by the US Food and Drug Administration (FDA). Design, Setting, and Participants: Retrospective cross-sectional study performed from June 2018 through October 2018 using publicly available data to determine (1) demographic characteristics of patients with advanced or metastatic cancer, (2) FDA data on checkpoint inhibitors approved from January 2011 throug

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  3. Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics

    Julianne D. Twomey, Baolin Zhang · 2021 · The AAPS Journal · 657 citations

    Immune checkpoint inhibitors (ICIs) are considered a new standard-of-care across many cancer indications. This review provides an update on ICIs approved by the Food and Drug Administration (FDA), with focus on monoclonal antibodies that target the programmed cell death 1 (PD-1) or its ligand, PD-1 ligand 1 (PD-L1), including information on their clinical indications and associated companion diagnostics. The information is further discussed with strategies for identifying predictive biomarkers to guide the clinical use of PD-1/PD-L1-targeted therapies.

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  5. Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors

    Rilan Bai, Zheng Lv, Dongsheng Xu, et al. · 2020 · Biomarker Research · 471 citations

    Although the clinical development of immune checkpoint inhibitors (ICIs) therapy has ushered in a new era of anti-tumor therapy, with sustained responses and significant survival advantages observed in multiple tumors, most patients do not benefit. Therefore, more and more attention has been paid to the identification and development of predictive biomarkers for the response of ICIs, and more in-depth and comprehensive understanding has been continuously explored in recent years. Predictive markers of ICIs efficacy have been gradually explored from the expression of intermolecular interactions within tumor cells to the expression of various molecules and cells in tumor microenvironment, and

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  6. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors.

    E. De Martin, J. Michot, B. Papouin, et al. · 2018 · Journal of hepatology · 403 citations

    BACKGROUND & AIMS Immunotherapy for metastatic cancer can be complicated by the onset of hepatic immune-related adverse events (IRAEs). This study compared hepatic IRAEs associated with anti-programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs). METHODS Among 536 patients treated with anti-PD-1/PD-L1 or CTLA-4 immunotherapies, 19 (3.5%) were referred to the liver unit for grade ≥3 hepatitis. Of these patients, nine had received anti-PD-1/PD-L1 and seven had received anti-CTLA-4 mAbs, in monotherapy or in combination with anti-PD-1. Liver investigations were undertaken in these 16 patients, including viral

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  7. Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy

    Matthew E. Griffin, Juliel Espinosa, Jessica L. Becker, et al. · 2021 · Science · 362 citations

    Abstract The antitumor efficacy of cancer immunotherapy has been correlated with specific species within the gut microbiota. However, molecular mechanisms by which these microbes affect host response to immunotherapy remain elusive. Here we show that specific members of the bacterial genus Enterococcus can promote anti-PD-L1 immunotherapy in mouse tumor models. The active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in non-protective E. faecalis was sufficient to promote antitumor activity of clinically approved checkpoint targets, and its activity required the peptidoglycan sensor Nod2. No

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  10. EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

    M. Kostine, A. Finckh, C. Bingham, et al. · 2020 · Annals of the Rheumatic Diseases · 251 citations

    Background Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management. Methods First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed. Results The overarching principles defined the role of rheumatologists in

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  11. Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired

    H. Marei, Anwarul Hasan, G. Pozzoli, et al. · 2023 · Cancer Cell International · 222 citations

    Cancer is still the leading cause of death globally. The approval of the therapeutic use of monoclonal antibodies against immune checkpoint molecules, notably those that target the proteins PD-1 and PD-L1, has changed the landscape of cancer treatment. In particular, first-line PD-1/PD-L1 inhibitor drugs are increasingly common for the treatment of metastatic cancer, significantly prolonging patient survival. Despite the benefits brought by immune checkpoint inhibitors (ICIs)-based therapy, the majority of patients had their diseases worsen following a promising initial response. To increase the effectiveness of ICIs and advance our understanding of the mechanisms causing cancer resistance,

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  12. Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer

    Jennifer L. Dine, RuthAnn Gordon, Yelena Shames, et al. · 2017 · Asia-Pacific Journal of Oncology Nursing · 214 citations

    Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mechanisms. The second half of the review discusses in greater depth immune checkpoint inhibitors that have recently demonstrated tremendous promise for the treatment of diverse solid tumor types, including

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  13. Cancer immunotherapy beyond immune checkpoint inhibitors

    Julian Andres Marin-Acevedo, Aixa Elena Soyano, Bhagirathbhai Dholaria, et al. · 2018 · Journal of Hematology & Oncology · 212 citations

    Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric mono

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  14. Introduction to checkpoint inhibitors and cancer immunotherapy

    Arlene H. Sharpe · 2017 · Immunological Reviews · 177 citations

    This article introduces a series of reviews covering Checkpoint Inhibitors and Cancer Immunotherapy appearing in Volume 276 of Immunological Reviews. Immune responses are regulated by an exquisite system of checks and balances that enable effective protective immunity and tolerance. A number of immunological checkpoints control cells of the innate and adaptive immune system that determine their function. Stimulatory checkpoint pathways promote activation of naive T cells, as well as effector, memory and regulatory T cell responses. Inhibitory checkpoint pathways limit the threshold for T cell activation and duration of immune responses, and have diverse effects that regulate resolution of in

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  15. Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy

    J. Lee, H. R. Kim, S. Ha · 2022 · Immune Network · 159 citations

    Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in wh

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  16. Immune Checkpoint inhibitors: An introduction to the next‐generation cancer immunotherapy

    Lucy Lee, Manish Gupta, Srikumar Sahasranaman · 2015 · The Journal of Clinical Pharmacology · 149 citations

    Activating the immune system to eliminate cancer cells and produce clinically relevant responses has been a long-standing goal of cancer research. Most promising therapeutic approaches to activating antitumor immunity include immune checkpoint inhibitors. Immune checkpoints are numerous inhibitory pathways hardwired in the immune system. They are critical for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues to minimize collateral tissue damage. Tumors regulate certain immune checkpoint pathways as a major mechanism of immune resistance. Because immune checkpoints are initiated by ligand-receptor interactions, blockad

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  18. Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors

    Elena Catanzaro, Manuel Beltrán-Visiedo, L. Galluzzi, et al. · 2024 · Cellular and Molecular Immunology · 115 citations

    While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction of patients are refractory to ICIs employed as standalone therapeutics, necessitating the development of combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest as combinatorial partners for ICIs, at least in part owing to their ability to initiate a tumor-targeting adaptive immune response. However, compared with either approach alone, combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity. Here, we discuss accumulating evidence on the therapeut

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  19. Immunotherapy in triple negative breast cancer: beyond checkpoint inhibitors

    Y. Abdou, A. Goudarzi, Jia Xin Yu, et al. · 2022 · NPJ Breast Cancer · 113 citations

    The development of immunotherapy agents has revolutionized the field of oncology. The only FDA-approved immunotherapeutic approach in breast cancer consists of immune checkpoint inhibitors, yet several novel immune-modulatory strategies are being actively studied and appear promising. Innovative immunotherapeutic strategies are urgently needed in triple negative breast cancer (TNBC), a subtype of breast cancer known for its poor prognosis and its resistance to conventional treatments. TNBC is more primed to respond to immunotherapy given the presence of more tumor infiltrating lymphocytes, higher PD-L1 expression, and higher tumor mutation burden relative to the other breast cancer subtypes,

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  20. Immune-checkpoint inhibitors for the treatment of metastatic melanoma: a model of cancer immunotherapy.

    P. Queirolo, A. Boutros, E. Tanda, et al. · 2019 · Seminars in cancer biology · 97 citations

    Melanoma has always been described as an immunogenic tumor. Despite that, until 2011 the standard of care in metastatic melanoma was chemotherapy, with low response rates and no clear impact on overall survival. Melanoma was the first cancer type to drive the use of immune-checkpoint inhibitors into clinical practice, which revolutionized the therapeutic paradigm not only in melanoma, but also in an increasing number of tumors. In this review, the preclinical bases and the main clinical studies that led to the approval of immune-checkpoint inhibitors in advanced melanoma will be described with insights on novel combinations of treatments and on prognostic and predictive biomarkers.

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  21. Sustained and targeted delivery of checkpoint inhibitors by metal-organic frameworks for cancer immunotherapy

    Shahad K. Alsaiari, S. Qutub, Shichao Sun, et al. · 2021 · Science Advances · 91 citations

    Delivery of antibodies using smart frameworks affords sustained and targeted activation of T cells for improved immunotherapy. The major impediments to the implementation of cancer immunotherapies are the sustained immune effect and the targeted delivery of these therapeutics, as they have life-threatening adverse effects. In this work, biomimetic metal-organic frameworks [zeolitic imidazolate frameworks (ZIFs)] are used for the controlled delivery of nivolumab (NV), a monoclonal antibody checkpoint inhibitor that was U.S. Food and Drug Administration–approved back in 2014. The sustained release behavior of NV-ZIF has shown a higher efficacy than the naked NV to activate T cells in hematolog

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  22. Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies

    I. Chyuan, C. Chu, P. Hsu · 2021 · Cancers · 62 citations

    Simple Summary Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy, and it has greatly expanded our knowledge of anticancer immunity and has introduced breakthroughs in cancer therapy. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. This review provides an overview of recent advances in cellular and molecular factors within the tumor microenvironment (TME) to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies for cancer immunotherapy. The in-depth exploration of complexity wi

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  23. Combination Cancer Immunotherapy of Nanoparticle-Based Immunogenic Cell Death Inducers and Immune Checkpoint Inhibitors

    Jing Qi, Feiyang Jin, Xiaoling Xu, et al. · 2021 · International Journal of Nanomedicine · 56 citations

    Abstract Cancer immunotherapy is a promising treatment strategy that aims to strengthen immune responses against cancer. However, the low immunogenicity of tumor cells and inhibition of effector T cells in the tumor immunosuppressive microenvironment remain two major challenges. Immunogenic cell death (ICD) inducers not only directly kill cancer cells but also increase the tumor immunogenicity and induce antitumor immune responses. Immune checkpoint inhibitors can alleviate the inhibition of immune cells. Significantly, the combination of ICD inducers and immune checkpoint inhibitors elicits a remarkable antitumor effect. Nanoparticles confer the ability to modulate systemic biodistribution

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  24. Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors

    Sama Rezasoltani, A. Yadegar, Hamid Asadzadeh Aghdaei, et al. · 2020 · Cancer Medicine · 56 citations

    The human gastrointestinal (GI) tract harbors gut microbiome, which plays a crucial role in preserving homeostasis at the intestinal host‐microbial interface. Conversely, specific gut microbiota may be altered during various pathological conditions and produce a number of toxic compounds and oncoproteins, in turn, to induce both inflammatory response and carcinogenesis. Recently, promising findings have been documented toward the implementation of certain intestinal microbiome in the next era of cancer biology and cancer immunotherapy. Notably, intestinal microbiota can cooperate with immune checkpoint inhibitors (ICIs) of its host, especially in enhancing the efficacy of programmed death 1

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