Program death-1 immune checkpoint and tumor microenvironment in malignant liver tumors

Moris, Demetrios; Rahnemai‐Azar, Amir A.; Zhang, Xu Feng; Ntanasis‐Stathopoulos, Ioannis; Tsilimigras, Diamantis I.; Chakedis, Jeffery; Argyrou, Chrysoula; Fung, John J.; Pawlik, Timothy M.

doi:10.1016/j.suronc.2017.08.005

Cited by 22 publications

(15 citation statements)

References 57 publications

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“…Liver transplantation has been associated with better 3-year (74.2% vs. 54.4%, p=0.02) and 5-year (62.5% vs. 35.6%, p<0.01) disease-free survival rates compared with Iiver resection (27). Other non-curative treatment options include radiofrequency ablation, transarterial chemoembolization and newer chemotherapeutic agents, including sorafenib and immune checkpoint inhibitors (7,(28)(29)(30)(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

The Epidemiology, Staging and Outcomes of Sarcomatoid Hepatocellular Carcinoma: A SEER Population Analysis

Giannis

Morsy

Geropoulos

et al. 2021

In Vivo

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Section: Discussionmentioning

confidence: 99%

The Epidemiology, Staging and Outcomes of Sarcomatoid Hepatocellular Carcinoma: A SEER Population Analysis

Giannis

Morsy

Geropoulos

et al. 2021

In Vivo

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“…Pembrolizumab has shown efficacy against HCC, and it was approved in 2017 for solid tumors with MMR-D/MSI-H including HCC and in 2018 for advanced HCC [13]. ICIs have been suggested to be used against PD-1/PD-L1-expressing HCC [14]. Our patient had two primary cancers, of which the colorectal tumor was MMR-D. Lynch syndrome is a condition due to germline mutations in MMR genes.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome

et al. 2020

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We here report on a 74-year-old man diagnosed with a pT3cN0 <i>BRAF</i>-mutated and mismatch repair-deficient adenocarcinoma in the colon ascendens and 3 liver metastases. After hemicolectomy, the patient received treatment with the PD-1 inhibitor pembrolizumab. Three weeks later (on day 22), laboratory tests showed leukocytosis and an increase in transaminases; immune checkpoint inhibitor (ICI)-induced hepatitis was suspected and prednisolone therapy was initiated. On day 29, the patient was acutely hospitalized due to dyspnea, somnolence and walking difficulties. Dysarthria, hoarseness, muscle pain and weakness had developed and the dose of prednisolone was increased. Serum levels of lactate dehydrogenase, creatine kinase and myoglobin were increased and ICI-induced myositis was suspected. Antibodies against acetylcholine receptor and titin were present, indicating myasthenia gravis. Eventually, bulbar myopathy developed, including dysarthria and dysphagia, and the patient could no longer attain saturation without oxygen. The patient was transferred to the intensive care unit, intubated and given methylprednisolone, intravenous immunoglobulins and infliximab. The patient developed carbon dioxide retention and died on day 39. Microscopical examination of the intercostal musculature, diaphragm, cervical musculature and tongue showed inflammatory infiltration and fibrosis consistent with a pronounced myositis. In the liver, microscopical examination did not show metastases from colorectal cancer but instead a hepatocellular cancer. The cause of death was determined as respiratory insufficiency due to polymyositis. In conclusion, ICIs may induce myositis combined with neurological immune-related adverse events. In patients developing muscle weakness and pain under ICI therapy, myositis should be suspected.

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“…It has been suggested that checkpoint inhibition could be useful in the treatment of HCC where there is expression of PD-1 and PD-L1 in the tumor microenvironment [3]. It is also suggested that high levels of PD-1 and PD-L1 expression may be useful as biomarkers to predict prognosis in patients with HCC [3]. Finkelmeier et al [4] demonstrated that high soluble PD-L1 in serum indicated a poor outcome in patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection

et al. 2020

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Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer, speculated to arise from hepatic progenitor cells, and with a worse prognosis than hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) levels may be one prognostic factor. It has been suggested that checkpoint inhibition might be useful in the treatment of HCC where there is an increased expression of PD-1 and PD-L1 in the microenvironment. Its effect on CHC is unknown. We report a case with a large CHC, which was radically resected, but the 53-yearold female patient subsequently developed pulmonary metastases. Histology demonstrated low-differentiated CHC without microsatellite instability. Treatment with sorafenib was started but was stopped due to angioedema. Under subsequent gemcitabine/cisplatin treatment, the metastatic disease progressed with rising AFP levels. A third-line treatment with pembrolizumab was then started, 2 mg/kg b.w. i.v. every third week for 6 months. This resulted in a radiologically complete remission of the pulmonary metastases and AFP levels were normalized (<10 μg/L) from a level of 1,790 μg/L before treatment. The patient developed immunerelated adverse events (AEs) including diarrhea and hepatitis. These AEs were successfully treated with prednisolone and mycophenolate mofetil, and they were eventually resolved. There are no signs of cancer recurrence neither in the liver nor in the lungs at 33 months after the start of the checkpoint inhibition treatment, and the patient is doing well. Further study is urgently needed on the role of checkpoint inhibition therapy in liver cancer. are responsible for the surgical care and M.P. and L.N. for the oncologic care of the patient. F.A. and J.S. for conception of the study and drafting the manuscript. L.S. is responsible for the pathology examination of the primary liver tumor and pulmonary metastases including histology, immunohistochemistry analyses of MSI. F.H. is responsible for the radiological examinations of the patient. All authors were involved in writing the final manuscript.

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Program death-1 immune checkpoint and tumor microenvironment in malignant liver tumors

Cited by 22 publications

References 57 publications

The Epidemiology, Staging and Outcomes of Sarcomatoid Hepatocellular Carcinoma: A SEER Population Analysis

The Epidemiology, Staging and Outcomes of Sarcomatoid Hepatocellular Carcinoma: A SEER Population Analysis

Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome

Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection

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