De-novo and acquired resistance to immune checkpoint targeting

Syn, Nicholas; Teng, Michele W.L.; Mok, Tony; Soo, Ross A.

doi:10.1016/s1470-2045(17)30607-1

Cited by 609 publications

(438 citation statements)

References 108 publications

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“…There is no approved immunotherapy treatment for BTC yet, but the past few years have been enlightening and the list of cancers which are being treated with these agents is fast-growing and future research may eventually lead to the development of immunotherapy for poor-prognostic tumour types. Nonetheless, the multiple complex autonomous and extrinsic mechanisms that govern de-novo and acquired resistance [61] to immune-modulatory agents remain an avenue for future scientific exploration. Moreover, the value of these agents in conjunction with chemotherapy or radiotherapy which may alter the immunogenicity of solid tumours warrants further study.…”

Section: Discussionmentioning

confidence: 99%

Biliary Tract Cancer: Implicated Immune-Mediated Pathways and Their Associated Potential Targets

Tariq¹,

Vogel²,

McNamara³

et al. 2018

Oncol Res Treat

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There is a well-established link between biliary tract cancers (BTC) and chronic inflammatory conditions such as primary sclerosing cholangitis, chronic cholecystitis, chronic cholelithiasis, liver fluke-associated infestations, and chronic viral hepatic infections. These associated risk factors highlight the potential for development of immune-modulatory agents in this poor-prognostic disease group with limited treatment options. Clinical trials have evaluated the role of immune cells, inflammatory biomarkers, vaccines, cytokines, adoptive cell therapy, and immune checkpoint inhibitors in patients with BTC. Although these have demonstrated the importance of the immune environment in BTC, currently none of the immune-based therapies have been approved for use in this disease group. The role of immunomodulatory agents is a developing field and has yet to find its way ‘from bench to bedside' in BTC.

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Section: Discussionmentioning

confidence: 99%

Biliary Tract Cancer: Implicated Immune-Mediated Pathways and Their Associated Potential Targets

Tariq¹,

Vogel²,

McNamara³

et al. 2018

Oncol Res Treat

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“…CTLA-4 is constitutively expressed in regulatory T-cells, but only upregulated in conventional T-cells after activation, a phenomenon which is particularly notable in cancers [28]. Despite its positive antitumor activity, patients specifically treated with CTLA-4 antibodies or in combination with checkpoint-blocking antibodies are at higher risk of immune-related adverse events (compared to the occurrence of adverse side effects in the treatment with PD-1 inhibitors), such as dermatologic, gastrointestinal, endocrine, or hepatic autoimmune reactions [29].…”

Section: Ctla-4 Inhibitorsmentioning

confidence: 99%

Implications of Immunotherapy in Hepatobiliary Tumors

2019

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Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death worldwide. Upon ineligibility for resection, liver transplantation, or locoregional therapies, sorafenib has been the only systemic treatment option of advanced HCC for more than a decade. Immunotherapy is an evolving HCC treatment option that has shown promise in treatment efficacy at an acceptable safety profile during several preceding phase I/II trials. Numerous clinical trials of immune checkpoint inhibitors (ICPIs) alone, in combination of two, or combined with other targeted or locoregional therapies are ongoing. Encouraging results of two-phase III trials testing pembrolizumab or nivolumab versus standard care therapy even resulted in Food and Drug Administration approval for second-line treatment of advanced HCC. ICPIs may open new avenues to the treatment of hepatobiliary tumors, alone or in combination.

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“…[86] Current researches and clinical trials mainly focus on the three steps of adaptive immune response. [86] Current researches and clinical trials mainly focus on the three steps of adaptive immune response.…”

Section: Immunotherapymentioning

confidence: 99%

“…These T cells are collected from patients' blood and activated either with genetic engineering (e.g., chimeric antigen receptor T cell therapy, CAR-T therapy) or by direct exposure to tumor antigens. [86,90] In the past 5 years, immunotherapy has drawn great attention in research and some modalities have been approved to be ap-plied in clinic. [89] However, the tumor microenvironment is highly immunosuppressive: cancer cells express receptors to protect themselves from being attacked by cytotoxic T cells, which are named as immune checkpoints.…”

Section: Immunotherapymentioning

confidence: 99%

“…The activated cytotoxic T cells (Tc) are then transfused back to the patients to track and attack cancer cells. [91] In the treatment of highly metastatic cancers, such as melanoma, [92] urothelial carcinoma, [86] and prostate cancer, [93] immunotherapy works wonders, even curing some cancers that were regarded as terminal illnesses in the past. [89] Therefore, another way to activate the immune system is to use antibodies to block these checkpoints, resulting in an enhanced immune response against tumor.…”

Section: Immunotherapymentioning

confidence: 99%

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Multifunctional Nanotherapeutics for Photothermal Combination Therapy of Cancer

Tian

Guo

Yang

2018

Advanced Therapeutics

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Recently, photothermal therapy (PTT) has demonstrated excellent results in the treatment of preclinical cancer models and thus attracted intensive interests from the research fields of material science, biochemistry, oncology, and pharmacy. Also, its combination with other cancer therapies shows great promise for clinical application: PTT is able to make up for the drawbacks of others and improve the prognosis through various synergistic effects. In these combination therapies, design of nanoscale multifunctional therapeutics is key to achieve enhanced or even synergistic therapeutic effect. Herein, the recent progress is summarized in the development of strategies involving combination of PTT with other cancer therapies, conventional or emerging, with increased efficacy. The highlight lies in integrating various functional units to form multifunctional nanomaterials that play the role of photothermal agents as well as other therapeutics in a combination therapy and the design of an effective targeted delivery system for them. Smart combination of therapies will undoubtedly improve the therapeutic efficacy and make a contribution to the advancement in fighting cancer.

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De-novo and acquired resistance to immune checkpoint targeting

Cited by 609 publications

References 108 publications

Biliary Tract Cancer: Implicated Immune-Mediated Pathways and Their Associated Potential Targets

Biliary Tract Cancer: Implicated Immune-Mediated Pathways and Their Associated Potential Targets

Implications of Immunotherapy in Hepatobiliary Tumors

Multifunctional Nanotherapeutics for Photothermal Combination Therapy of Cancer

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