scholarly journals Clinical research progress of immune checkpoint inhibitors in treatment of primary liver cancer

2020 ◽  
Vol 28 (14) ◽  
pp. 605-616
Author(s):  
Jin-Zhi Zhang ◽  
Yu-Zhu Ma ◽  
Jia-Lin Gu ◽  
Jie-Ge Huo
Keyword(s):  
Liver Cancer ◽  
Clinical Research ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Research Progress

scholarly journals Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1078 ◽  
Author(s):  
Amit Mahipal ◽  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Alexander Lim ◽  
Richard Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Hepatic Reserve ◽  
Dismal Prognosis ◽  
United States Food

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with dismal prognosis when diagnosed at advanced stages. Surgical resection of the primary tumor or orthotropic liver transplantation serves as a potential curative option. However, this approach is highly dependent on the hepatic reserve and baseline functional status of the patient. Liver directed therapies such as portal vein embolization (PVE), trans-arterial chemoembolization (TACE), and systemic chemotherapy are employed in non-surgical candidates. Sorafenib was the only approved systemic therapeutic agent for almost a decade until the recent approval of lenvatinib by the United States Food and Drug Administration (FDA) as an alternate first-line agent. Regorafenib, nivolumab, pembrolizumab and cabozantinib are approved by the FDA as second-line agents in patients who failed or could not tolerate sorafenib. Ramucirumab was recently FDA approved for the subset of patients that have high alfa-fetoprotein levels (>400 ng/mL). A better understanding of tumorigenesis and encouraging clinical trial results that evaluated immune-checkpoint inhibitors opened doors for immunotherapy in HCC. Immune checkpoint inhibitors have demonstrated a prolonged median overall and progression-free survival in a subset of patients with HCC. On-going translational and clinical research will hopefully provide us with a better understanding of tumor markers, genetic aberrations and other factors that determine the immunotherapy response in HCC. In this review, we sought to summarize the potential role and future directions of immunotherapy in the management of HCC.

scholarly journals Clinical Research on the Mechanisms Underlying Immune Checkpoints and Tumor Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xi-Yang Tang ◽  
An-Ping Shi ◽  
Yan-Lu Xiong ◽  
Kai-Fu Zheng ◽  
Yu-Jian Liu ◽  
...  
Keyword(s):  
Clinical Research ◽  
Immune Checkpoint ◽  
Tumor Metastasis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Immune Checkpoints ◽  
Metastatic Tumors ◽  
Non Hodgkin Lymphoma ◽  
Immunological Mechanisms

This study highlights aspects of the latest clinical research conducted on the relationship between immune checkpoints and tumor metastasis. The overview of each immune checkpoint is divided into the following three sections: 1) structure and expression; 2) immune mechanism related to tumor metastasis; and 3) clinical research related to tumor metastasis. This review expands on the immunological mechanisms of 17 immune checkpoints, including TIM-3, CD47, and OX-40L, that mediate tumor metastasis; evidence shows that most of these immune checkpoints are expressed on the surface of T cells, which mainly exert immunomodulatory effects. Additionally, we have summarized the roles of these immune checkpoints in the diagnosis and treatment of metastatic tumors, as these checkpoints are considered common predictors of metastasis in various cancers such as prostate cancer, non-Hodgkin lymphoma, and melanoma. Moreover, certain immune checkpoints can be used in synergy with PD-1 and CTLA-4, along with the implementation of combination therapies such as LIGHT-VTR and anti-PD-1 antibodies. Presently, most monoclonal antibodies generated against immune checkpoints are under investigation as part of ongoing preclinical or clinical trials conducted to evaluate their efficacy and safety to establish a better combination treatment strategy; however, no significant progress has been made regarding monoclonal antibody targeting of CD28, VISTA, or VTCN1. The application of immune checkpoint inhibitors in early stage tumors to prevent tumor metastasis warrants further evidence; the immune-related adverse events should be considered before combination therapy. This review aims to elucidate the mechanisms of immune checkpoint and the clinical progress on their use in metastatic tumors reported over the last 5 years, which may provide insights into the development of novel therapeutic strategies that will assist with the utilization of various immune checkpoint inhibitors.

scholarly journals Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao-Tian Liu ◽  
Meng-Jie Jiang ◽  
Zhu-Jian Deng ◽  
Le Li ◽  
Jian-Li Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Research Progress ◽  
T Cell Signaling ◽  
Existing Problems ◽  
Programmed Death ◽  
New Treatment

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

scholarly journals Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Chang Liu ◽  
Miao Wang ◽  
Changli Xu ◽  
Bo Li ◽  
Juxiang Chen ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Bone Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Basic Research ◽  
Research Progress ◽  
Immunological Mechanism ◽  
Carcinoma Prostate ◽  
Checkpoint Inhibitor Therapy

The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.

scholarly journals Application of Immunotherapy in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Lele Miao ◽  
Zhengchao Zhang ◽  
Zhijian Ren ◽  
Yumin Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Therapy ◽  
Immune Responses ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Research Progress ◽  
Tumor Vaccines ◽  
Immunosuppressive Microenvironment

Hepatocellular carcinoma is one of the most common malignancies globally. It not only has a hidden onset but also progresses rapidly. Most HCC patients are already in the advanced stage of cancer when they are diagnosed, and have even lost the opportunity for surgical treatment. As an inflammation-related tumor, the immunosuppressive microenvironment of HCC can promote immune tolerance through a variety of mechanisms. Immunotherapy can activate tumor-specific immune responses, which brings a new hope for the treatment of HCC. At the present time, main immunotherapy strategies of HCC include immune checkpoint inhibitors, tumor vaccines, adoptive cell therapy, and so on. This article reviews the application and research progress of immune checkpoint inhibitors, tumor vaccines, and adoptive cell therapy in the treatment of HCC.

scholarly journals PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 558 ◽  
Author(s):  
Alessandro Rizzo ◽  
Angela Dalia Ricci ◽  
Giovanni Brandi
Keyword(s):  
Biliary Tract ◽  
Anticancer Agents ◽  
Biliary Tract Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Tract Cancer ◽  
Predictors Of Response ◽  
Tumor Mutational Burden

Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers.

scholarly journals Research progress in immune checkpoint inhibitors for lung cancer in China

2021 ◽  
Vol 13 ◽  
pp. 175883592110298
Author(s):  
Jiadi Gan ◽  
Yihua Huang ◽  
Wenfeng Fang ◽  
Li Zhang
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Research Progress ◽  
First Line ◽  
Future Directions ◽  
Programmed Death ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) have come to play an increasingly prominent role in the treatment of lung cancer, and some are recommended as a first-line treatment for late-stage non-small-cell lung cancer, either as a monotherapy or in combination with chemotherapy. Accordingly, the indications of Food and Drug Administration-approved ICIs have increased. In this background, China has implemented various policies to encourage and accelerate the marketing of domestic and imported innovative antitumor drugs. Eight ICIs have been approved in China. Among these, four imported programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have received approval for six indications, and one domestic PD-1 inhibitor has received approval for one indication for lung cancer in 2018. Numerous clinical trials of ICIs for lung cancer are underway in China. This review aims to summarize the recent advances and future directions of ICIs, including PD-1 inhibitors, PD-L1 inhibitors, cytotoxic T lymphocyte-associated antigen-4 inhibitors, bi-specific antibodies, and a novel inhibitor of T-cell immune-receptor with Ig and immunoreceptor tyrosine-based inhibitory motif domains in immunotherapies for lung cancer in China.

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