The emerging use of immune checkpoint blockade in the adjuvant setting for solid tumors: a review

Immunotherapy ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1409-1422 ◽  
Author(s):  
Elissar Moujaess ◽  
Fady Gh Haddad ◽  
Roland Eid ◽  
Hampig Raphael Kourie
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Adjuvant Setting ◽  
Lung Cancers ◽  
Metastatic Setting ◽  
Postoperative Setting

The use of immune checkpoint inhibitors has been approved in the advanced and metastatic setting for many types of solid tumors. Nonetheless, their role in the adjuvant setting is limited to the treatment of surgically resected melanoma. Ipilimumab was the first immune checkpoint inhibitor approved for this indication, followed by nivolumab and pembrolizumab. Many ongoing trials are evaluating these molecules in the postoperative setting, alone or in combination with other therapies. Preliminary results are promising regarding the treatment of other cutaneous tumors, lung cancers, head and neck squamous cell carcinomas, bladder cancer and renal cell carcinomas. Some data assessing their use for the adjuvant treatment of esophageal, colorectal, ovarian cancer and other solid tumors are similarly emerging.

scholarly journals Application of Immune Checkpoint Inhibitors in the Treatment of Cholangiocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110399
Author(s):  
Fan-li Zeng ◽  
Jing-fang Chen
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Malignant Tumors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
General Term ◽  
Distal Cholangiocarcinoma ◽  
Poor Outcomes ◽  
Defective Mismatch Repair

Cholangiocarcinoma is a general term for intrahepatic and extrahepatic malignant tumors deriving in the biliary system. According to the location, it is divided into intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma. Progressive cholangiocarcinoma yields poor outcomes with radiotherapy; therefore, there is an urgent need for new therapeutic breakthroughs. Immune checkpoint inhibitor (ICI) therapy brings the treatment for cancer into a new field, with the use of drugs targeting PD-1/PD-L1 and CTLA-4 considerably extending the survival of patients with melanoma, lung cancer, and other solid tumors. The FDA has approved the application of pembrolizumab for solid tumors with high microsatellite instability and defective mismatch repair, including cholangiocarcinoma. Moreover, the combination of ICIs with chemotherapy and radiation therapy showed good promise. The aim of the present study was to review the application of ICIs in the treatment of cholangiocarcinoma and to summarize the reported individualized immunotherapy-based protocols and ongoing clinical trials for clinical reference.

scholarly journals Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianyang Fu ◽  
Wang-Zhong Li ◽  
Nicole A. McGrath ◽  
Chunwei Walter Lai ◽  
Gagandeep Brar ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
High Grade ◽  
Liver Cancers ◽  
Grade 3

BackgroundOverall risks of hepatotoxicity with immune checkpoint inhibitors (ICIs) have yet to be compared in primary liver cancers to other solid tumors.MethodsWe reviewed data from the PubMed, Embase, and Scopus databases, and assessed the risk of hepatotoxicity associated with ICIs.ResultsA total of 117 trials were eligible for the meta‐analysis, including 7 trials with primary liver cancers. The most common hepatotoxicity was ALT elevation (incidence of all grade 5.29%, 95% CI 4.52-6.20) and AST elevation (incidence of all grade 5.88%, 95% CI 4.96-6.97). The incidence of all grade ALT and AST elevation was 6.01% and 6.84% for anti-PD‐1 (95% CI 5.04-7.18/5.69-8.25) and 3.60% and 3.72% for anti-PD-L1 (95% CI 2.72-4.76/2.82-4.94; p< 0.001/p<0.001). The incidence of ≥ grade 3 ALT and AST elevation was 1.54% and 1.48% for anti-PD‐1 (95% CI 1.19-1.58/1.07-2.04) and 1.03% and 1.08% for anti-PD-L1 (95% CI 0.71-1.51/0.80-1.45; p= 0.002/p<0.001). The incidence of all grade ALT and AST elevation was 13.3% and 14.2% in primary liver cancers (95% CI 11.1-16.0 and 9.93-20.36) vs. 4.92% and 5.38% in other solid tumors (95% CI 4.21-5.76 and 4.52-5.76 in other solid tumors; p <0.001/p<0.001).ConclusionOur study indicates that anti-PD-1 is associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to anti-PD-L1, and primary liver cancers are associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to other solid tumors.

scholarly journals Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors

2019 ◽  
Vol 17 (6) ◽  
pp. 750-757 ◽  
Author(s):  
Laura C. Kennedy ◽  
Shailender Bhatia ◽  
John A. Thompson ◽  
Petros Grivas
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Metastatic Setting ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Types

The use of immune checkpoint inhibitors (ICIs) is rapidly expanding to the treatment of many cancer types, both in the metastatic setting and as an adjuvant to other therapies. Clinical trials using ICIs have largely excluded patients with preexisting autoimmune diseases due to concerns for increased toxicity. However, emerging evidence shows that ICIs may be considered in some patients with autoimmunity. This review discusses the commonalities between clinical autoimmune diseases and ICI-induced immunotherapy-related adverse events, and summarizes the existing case series that describes patients with solid tumors who have a preexisting autoimmune disease. This review also discusses which patients with autoimmunity could be considered reasonable candidates for ICI therapy.

scholarly journals Immune checkpoint blockade therapy in head and neck cancer: a review

2018 ◽  
Vol 8 (2) ◽  
pp. 30-33
Author(s):  
Shajedul Islam ◽  
Md Shahed Rafi Pavel ◽  
Syed Taufiqul Islam ◽  
Nazmus Shalehin ◽  
Shahed Jahan Babu
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Immune Checkpoint Blockade ◽  
Current Review

Head and neck cancer (HNC) is a common malignant tumor, carrying a poor prognosis, and despite advances in oncology, this rate has not improved significantly for decades. It has recently been evaluated that the immunologic checkpoint inhibitors become a novel promising strategic immunotherapy in the treatment of metastatic cancer. Therefore, our current review article will discuss the biological role and impact of the immune checkpoint inhibitor in HNC. Update Dent. Coll. j: 2018; 8 (2): 30-33

scholarly journals Advances in immune checkpoint inhibitors for hepatocellular carcinoma

2021 ◽  
Vol 21 (2) ◽  
pp. 139-145
Author(s):  
Ji Won Han ◽  
Su-Hyung Park
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Rational Design ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
New Era ◽  
Common Cancer

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the second leading cause of cancer-related death worldwide. Although recent advances in immune checkpoint inhibitor-based immunotherapy have initiated a new era for advanced HCC treatment, the majority of HCC patients receiving immune checkpoint blockades do not derive clinical benefit. Thus, there remains an urgent need for novel immunotherapeutic strategies with improved therapeutic efficacy. Here we review recent studies of immune checkpoint blockade in HCC, providing the necessary basis for the rational design of immunotherapy.

scholarly journals Enterococcus peptidoglycan remodeling promotes immune checkpoint inhibitor therapy

2020 ◽  
Author(s):  
Matthew E. Griffin ◽  
Juliel Espinosa ◽  
Jessica L. Becker ◽  
Jyoti K. Jha ◽  
Gary R. Fanger ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Immune Checkpoint ◽  
Molecular Mechanisms ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Mouse Tumor ◽  
Peptidoglycan Hydrolases ◽  
Checkpoint Inhibitor Therapy ◽  
Specific Species

AbstractThe 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. Notably, SagA-engineered probiotics or synthetic muropeptides also promoted checkpoint inhibitor antitumor activity. Our data suggest that microbiota species with unique peptidoglycan remodeling activity may enhance immunotherapy and could be leveraged for next-generation adjuvants.One Sentence SummaryA conserved family of secreted NlpC/p60 peptidoglycan hydrolases from Enterococcus promote antitumor activity of immune checkpoint inhibitors.

Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Liver Cancers ◽  
First Line Treatment

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]

Immune checkpoint inhibitor sensitivity of DNA repair deficient tumors

Immunotherapy ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 1205-1213
Author(s):  
Pauline Rochefort ◽  
Françoise Desseigne ◽  
Valérie Bonadona ◽  
Sophie Dussart ◽  
Clélia Coutzac ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Immune Checkpoint ◽  
Genome Stability ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Excision Repair ◽  
Checkpoint Inhibitors ◽  
Repair Deficiency ◽  
Dna Repair Deficiency

Faithful DNA replication is necessary to maintain genome stability and implicates a complex network with several pathways depending on DNA damage type: homologous repair, nonhomologous end joining, base excision repair, nucleotide excision repair and mismatch repair. Alteration in components of DNA repair machinery led to DNA damage accumulation and potentially carcinogenesis. Preclinical data suggest sensitivity to immune checkpoint inhibitors in tumors with DNA repair deficiency. Here, we review clinical studies that explored the use of immune checkpoint inhibitor in patient harboring tumor with DNA repair deficiency.

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