Harnessing the Immune System as a Therapeutic Tool in Virus-Associated Cancers

Santana-Dávila, Rafael; Bhatia, Shailender; Chow, Laura Q.M.

doi:10.1001/jamaoncol.2016.4574

Cited by 17 publications

(6 citation statements)

References 55 publications

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“…A number of chronic infections, such as liver-fluke disease, viral hepatitis B and C, and bacterial pyogenic cholangitis, are established risk factors for cholangiocarcinoma 1,149 . Notably, immune- checkpoint inhibitors and other immunotherapies have shown promising efficacy in other tumours commonly associated with viral infections, such as head and neck cancer, Hodgkin lymphoma, Merkel-cell carcinoma, and HCC 150 , and this relationship is thought to be mediated, in part, by the presentation of non-self or neoantigens associated with viral infections 150–152 . Notably, transcriptome sequencing and clustering of gene-expression profiles revealed a subgroup of patients with cholangiocarcinomas with a high mutational load, resulting in abundant tumour-specific neoantigens, and enrichment for expression of immune-related genes, including genes encoding inhibitory immune-checkpoint proteins 92 .…”

Section: Emerging Molecularly-directed Therapiesmentioning

confidence: 99%

Cholangiocarcinoma — evolving concepts and therapeutic strategies

et al. 2017

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Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external-beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma.

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Section: Emerging Molecularly-directed Therapiesmentioning

confidence: 99%

Cholangiocarcinoma — evolving concepts and therapeutic strategies

et al. 2017

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“…Promising results have been reported through the administration of immunotherapies in malignancies commonly associated with viral infections [109] and the rationale for this might be the presentation of neoantigens associated with viral infections [110,111]. Liver-fluke disease, viral hepatitis B and C, and bacterial pyogenic cholangitis are all established risk factors for CCA [112], thus the subgroup of patients with CCA with underlying chronic viral infections or chronic inflammation, like sclerosing cholangitis, might take the most advantage by the administration of immunotherapy.…”

Section: Combo-strategiesmentioning

confidence: 99%

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Massironi

Pilla

Elvevi

et al. 2020

Cells

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Cholangiocarcinoma (CCA) represents a disease entity that comprises a heterogeneous group of biliary malignant neoplasms, with variable clinical presentation and severity. It may be classified according to its anatomical location and distinguished in intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), each subtype implying distinct epidemiology, biology, prognosis, and strategy for clinical management. Its incidence has increased globally over the past few decades, and its mortality rate remains high due to both its biological aggressiveness and resistance to medical therapy. Surgery is the only potentially curative treatment and is the standard approach for resectable CCA; however, more than half of the patients have locally advanced or metastatic disease at presentation. For patients with unresectable CCA, the available systemic therapies are of limited effectiveness. However, the advances of the comprehension of the complex molecular landscape of CCA and its tumor microenvironment could provide new keys to better understand the pathogenesis, the mechanisms of resistance and ultimately to identify promising new therapeutic targets. Recently, clinical trials targeting isocitrate dehydrogenase (IDH)-1 mutations and fibroblast growth factor receptor (FGFR)-2 fusions, as well as immunotherapy showed promising results. All these new and emerging therapeutic options are herein discussed.

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“…Lymphocyte populations within whole blood, such as B, T, and NK cells, are specialized cells of the adaptive and innate immune systems. Targeting these cells to modulate immunity is of growing interest, with several monoclonal antibody products marketed to suppress aberrant immune responses. − We therefore assessed whether thiol-reactive PDS star polymer NPs could interact with lymphocyte populations within fresh human blood (Figure ). The gating strategy is shown in Figure A.…”

Section: Resultsmentioning

confidence: 99%

Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components

Glass

Rose

et al. 2017

ACS Appl. Mater. Interfaces

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Directing nanoparticles to specific cell types using nonantibody-based methods is of increasing interest. Thiol-reactive nanoparticles can enhance the efficiency of cargo delivery into specific cells through interactions with cell-surface proteins. However, studies to date using this technique have been largely limited to immortalized cell lines or rodents, and the utility of this technology on primary human cells is unknown. Herein, we used RAFT polymerization to prepare pyridyl disulfide (PDS)-functionalized star polymers with a methoxy-poly(ethylene glycol) brush corona and a fluorescently labeled cross-linked core using an arm-first method. PDS star polymers were examined for their interaction with primary human blood components: six separate white blood cell subsets, as well as red blood cells and platelets. Compared with control star polymers, thiol-reactive nanoparticles displayed enhanced association with white blood cells at 37 °C, particularly the phagocytic monocyte, granulocyte, and dendritic cell subsets. Platelets associated with more PDS than control nanoparticles at both 37 °C and on ice, but they were not activated in the duration examined. Association with red blood cells was minor but still enhanced with PDS nanoparticles. Thiol-reactive nanoparticles represent a useful strategy to target primary human immune cell subsets for improved nanoparticle delivery.

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Harnessing the Immune System as a Therapeutic Tool in Virus-Associated Cancers

Cited by 17 publications

References 55 publications

Cholangiocarcinoma — evolving concepts and therapeutic strategies

Cholangiocarcinoma — evolving concepts and therapeutic strategies

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Thiol-Reactive Star Polymers Display Enhanced Association with Distinct Human Blood Components

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