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Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2233-2240页

作者： Joaquina Martínez-Galán Cristina Jiménez-Luna Isabel Rodriguez Elisabeth Maza Carlos García-Collado Antonio Rodríguez-Fernández Javier Luis López-Hidalgo Octavio Caba Department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain Instituto de Investigación Biosanitaria Ibs.GranadaGranada 18012Spain Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Pharmacogenetics Unit Virgen de las Nieves University HospitalGranada 18014Spain Department of Medicina Nuclear Virgen de las Nieves University HospitalGranada 18014Spain Department of Anatomía Patológica Virgen de las Nieves University HospitalGranada 18014Spain

BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival *** is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor *** describe a case of metastatic PDAC effectively treated with *** SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus *** nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung *** immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor *** patient showed a complete metabolic response that was maintained throughout the *** patient continues to be disease-free at 5.6 years since the start of *** These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic *** our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative *** studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

关键词： Pancreatic ductal adenocarcinoma Lung cancer Immunotherapy Pembrolizumab programmed cell death protein-1 Case report

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Specific CD8^+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis

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World Journal of Gastroenterology 2016年第28期22卷 6469-6483页

作者： Elia Moreno-Cubero Juan-Ramón Larrubia Translational Hepatology Unit Guadalajara University Hospital University of Alcalá Department of Biology of Systems University of Alcalá Department of Medicine and Medical Specialties University of Alcalá

Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8+ T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.

关键词： Hepatocellular carcinoma CD8+ T cells Immune checkpoint modulation Chronic viral hepatitis Cytotoxic T-lymphocyte antigen-4 programmed cell death protein-1

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Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 772-798页

作者： Alexa R Weingarden Samuel J S Rubin John Gubatan Division of Gastroenterology and Hepatology Department of MedicineStanford UniversityRedwood CityCA 94063United States Stanford University School of Medicine Stanford UniversityRedwood CityCA 94063United States

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer *** re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)***,these therapies can also induce autoimmune-like side effects in healthy tissue across the *** of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI *** also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology.

关键词： Immune checkpoint inhibitors Cytotoxic T-lymphocyte antigen 4 programmed cell death protein-1 Inflammatory bowel disease Gastrointestinal cancer

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Immune checkpoint blockade therapies for HCC: current status and future implications

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Hepatoma Research 2019年第9期5卷 1-17页

作者： Ritu Shrestha Kim R.Bridle Darrell H.G.Crawford Aparna Jayachandran The University of Queensland Faculty of MedicineBrisbaneQueensland 4120Australia Gallipoli Medical Research Institute Greenslopes Private HospitalBrisbaneQueensland 4120Australia

Hepatocellular carcinoma(HCC)is the most lethal and common type of liver cancer with limited treatment options at the advanced *** use of immune checkpoint inhibitor(ICI)based immunotherapy is exponentially increasing in the treatment of patients with advanced solid *** expression of immune checkpoints on tumor cells leading to lower activity of T-cells is one of the major mechanisms of immune *** blockade immunotherapies with antibodies against PD-1,PD-L1 or CTLA-4 are being investigated in clinical trials in HCC *** have improved survival in patients with inoperable advanced stage HCC where other curative treatments are not ***,the response rates remain low with only a small subset of patients responding to this *** is an unmet need to identify predictive markers to select those HCC patients who would benefit from ICI ***,epithelial-to-mesenchymal transition(EMT),a major process driving HCC invasion and metastasis by regulating the phenotypic cellular switching from epithelial to mesenchymal state,has been implicated as a resistance mechanism associated with ICI *** role of EMT as a regulator of immune checkpoint molecule in HCC is just ***,the consequence of EMT as a resistance mechanism in HCC patients undergoing ICI treatments remains *** this review,we summarize the recent clinical studies with ICIs in HCC and highlight the trials underway featuring novel monotherapies and combinatorial approaches based on immune and non-immune *** will discuss the ongoing efforts to discover new immune checkpoint molecules in HCC as potential drug *** also highlight the role of EMT in facilitating therapy resistance in HCC treated with ICIs and discuss potential strategies to circumvent resistance in ICI treated HCC patients.

关键词： Hepatocellular carcinoma immunotherapy immune checkpoint inhibitors epithelial-to-mesenchymal transition programmed cell death protein-1 programmed death-ligand 1 resistance

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