scholarly journals Dynamic and specific immune responses against multiple tumor antigens were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy

2017 ◽  
Vol 15 (1) ◽  
Author(s):  
Yanyan Han ◽  
Yeting Wu ◽  
Chou Yang ◽  
Jing Huang ◽  
Yabing Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Responses ◽  
Tumor Antigens ◽  
Multiple Tumor

scholarly journals Cancer Vaccines: Adjuvant Potency, Importance of Age, Lifestyle, and Treatments

2021 ◽  
Vol 11 ◽  
Author(s):  
Stefania Cuzzubbo ◽  
Sara Mangsbo ◽  
Divya Nagarajan ◽  
Kinana Habra ◽  
Alan Graham Pockley ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Careful Consideration ◽  
Immune Functions ◽  
Mineral Salts ◽  
Functional Changes ◽  
Multiple Tumor ◽  
Novel Technologies

Although the discovery and characterization of multiple tumor antigens have sparked the development of many antigen/derived cancer vaccines, many are poorly immunogenic and thus, lack clinical efficacy. Adjuvants are therefore incorporated into vaccine formulations to trigger strong and long-lasting immune responses. Adjuvants have generally been classified into two categories: those that ‘depot’ antigens (e.g. mineral salts such as aluminum hydroxide, emulsions, liposomes) and those that act as immunostimulants (Toll Like Receptor agonists, saponins, cytokines). In addition, several novel technologies using vector-based delivery of antigens have been used. Unfortunately, the immune system declines with age, a phenomenon known as immunosenescence, and this is characterized by functional changes in both innate and adaptive cellular immunity systems as well as in lymph node architecture. While many of the immune functions decline over time, others paradoxically increase. Indeed, aging is known to be associated with a low level of chronic inflammation—inflamm-aging. Given that the median age of cancer diagnosis is 66 years and that immunotherapeutic interventions such as cancer vaccines are currently given in combination with or after other forms of treatments which themselves have immune-modulating potential such as surgery, chemotherapy and radiotherapy, the choice of adjuvants requires careful consideration in order to achieve the maximum immune response in a compromised environment. In addition, more clinical trials need to be performed to carefully assess how less conventional form of immune adjuvants, such as exercise, diet and psychological care which have all be shown to influence immune responses can be incorporated to improve the efficacy of cancer vaccines. In this review, adjuvants will be discussed with respect to the above-mentioned important elements.

scholarly journals Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000200 ◽  
Author(s):  
Shibin Qu ◽  
Tejaswi Worlikar ◽  
Amy E Felsted ◽  
Anutosh Ganguly ◽  
Megan V Beems ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Thermal Ablation ◽  
Tumor Antigens ◽  
Immune Cell ◽  
Checkpoint Inhibition ◽  
Non Invasive ◽  
Adaptive Immune ◽  
The Impact

BackgroundDeveloping the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens.MethodsImmunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection.ResultsHistotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma.ConclusionsThese preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy.

scholarly journals Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 678 ◽  
Author(s):  
Adrien Procureur ◽  
Audrey Simonaggio ◽  
Jean-Emmanuel Bibault ◽  
Stéphane Oudard ◽  
Yann-Alexandre Vano
Keyword(s):  
Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Mitotic Cell ◽  
Immunogenic Cell Death ◽  
Dna Damages ◽  
Multiple Tumor ◽  
Tumor Types

The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed.

Serum-derived exosomes function as tumor antigens in patients with advanced hepatocellular carcinoma

2021 ◽  
Vol 134 ◽  
pp. 210-217
Author(s):  
Shengbin Shi ◽  
Lei Wang ◽  
Cuijuan Wang ◽  
Jun Xu ◽  
Zuoxing Niu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Antigens ◽  
Advanced Hepatocellular Carcinoma

Radioembolization for Rare Metastatic Disease

2021 ◽  
Author(s):  
Andrew S. Niekamp ◽  
Govindarajan Narayanan ◽  
Brian J. Schiro ◽  
Constantino Pena ◽  
Alex Powell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Metastatic Colorectal Cancer ◽  
Treatment Modality ◽  
Treatment Options ◽  
Efficacy And Safety ◽  
Multiple Tumor ◽  
Tumor Types ◽  
Hepatic Malignancies ◽  
Yttrium 90

AbstractRadioembolization has become a widespread treatment modality for both primary and metastatic hepatic malignancies. Although the majority of data and indication for yttrium-90 radioembolization have been for hepatocellular carcinoma and metastatic colorectal cancer, radioembolization with yttrium-90 has rapidly expanded into the treatment options for multiple tumor types with metastases to the liver. This article reviews the clinical data and expanding utilization of radioembolization for rare metastatic diseases with an emphasis on efficacy and safety.

scholarly journals Targeting Tumor Antigens to Secreted Membrane Vesicles In vivo Induces Efficient Antitumor Immune Responses

2008 ◽  
Vol 68 (4) ◽  
pp. 1228-1235 ◽  
Author(s):  
Ingrid S. Zeelenberg ◽  
Matias Ostrowski ◽  
Sophie Krumeich ◽  
Angélique Bobrie ◽  
Carolina Jancic ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Antigens ◽  
Membrane Vesicles

Roles of Immune Cells in the Concurrence of Echinococcus Granulosus Infection and Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Aimaiti Yasen ◽  
Bo Ran ◽  
Maolin Wang ◽  
Guodong Lv ◽  
Renyong Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Echinococcus Granulosus ◽  
Immune Cells ◽  
Hepg2 Cells ◽  
Control Group ◽  
Cell Markers ◽  
Hepg2 Cell Lines

Abstract Background/aims: Immune cells are pivotal players in the immune responses against both parasitic infection and malignancies. Substantial evidence demonstrated that there may exist possible relationship between Echinococcus granulosus (E.granulosus) infection and hepatocellular carcinoma (HCC) development. Thus, this study aimed to observe crucial roles of immune cells in the formation of subcutaneous lesions after transplanting HepG2 cell lines with or without E.granulosus protoscoleces (PSCs).Methods: HepG2 cell lines were subcutaneously injected into nude mice in the control group. In the co-transplantation group, HepG2 cells were subcutaneously co-injected with high dosage of E.granulosus PSCs. From the 25th day of transplantation, volume of subcutaneous lesions was measured every four days, which were removed at the 37th day for further studies. Basic pathological and functional changes were observed. Moreover, expression of Ki67, Bal-2, Caspase3, α-smooth muscle actin (α-SMA), T cell markers (CD3, CD4, CD8), PD1/PD-L1, nature killer (NK) cell markers (CD16, CD56) were further detected by immunohistochemistry.Results: Subcutaneous lesions were gradually increased in volume and there occurred pathologically heterogeneous tumor cells, which were more significant in the co-transplantation group. Compared to the control group, expression of proliferation markers Ki67 and Bcl-2 was at higher levels in the co-transplantation group. Reversely, apoptotic marker Caspase3 was highly detected in the control group, suggesting promoting effects of E.granulosus PSCs on HCC development. Interestingly, subcutaneous lesions of the co-transplantation group were more functional in synthesizing and storing glycogen. Collagen and α-SMA+ cells were also at higher levels in the co-transplantation group than those in the control group. Most importantly, co-transplantation of HepG2 cells with E.granulosus PSCs led to significant increase in the expression of T cell markers (CD3, CD4 and CD8), immune inhibitory checkpoint PD1/PD-L1 and NK cells markers (CD16 and CD56). Conclusions: E.granulosus may have promoting effects on HCC development, which was closely associated with the immune responses of T cells and NK cells.

scholarly journals The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ling Wei ◽  
Xingwu Wang ◽  
Liyan Lv ◽  
Jibing Liu ◽  
Huaixin Xing ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Multiple Tumor ◽  
Nucleolar Rnas

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.

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