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Human endogenous retroviruses and cancer

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Cancer Biology & Medicine 2016年第4期13卷 483-488页

作者： María Gonzalez-Cao Paola Iduma Niki Karachaliou mariacarmela santarpia Julià Blanco Rafael Rosell Translational Cancer Research Unit Instituto Oncologico Dr Rosell Quiron Dexeus University Hospital Barcelona 08028 Spain AIDS Research Institute Hospital Universitari Germans Trias i Pujol Badalona 08028 Spain Medical Oncology Unit Human Pathology Department University of Messina Messina 98122 Italy UVIC-UCC Catalunya 08500 Spain Cancer Biology &Precision Medicine Program Catalan Institute of Oncology Germans Trias I Pujol Health Sciences Institute and Hospital Campus Can Ruti Badalona 08916 Spain Fundacion Molecular Oncology Research Barcelona 08028 Spain

Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.

关键词： HERVs cancer interferon immunotherapy

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

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Cancer Biology & Medicine 2015年第2期12卷 79-86页

作者： Niki Karachaliou Maria Gonzalez Cao Cristina Teixidó Santiago Viteri Daniela Morales-Espinosa mariacarmela santarpia Rafael Rosell Instituto Oncológico Dr Rosell Quiron Dexeus University Hospital Pangaea Biotech Medical Oncology Unit Human Pathology Department University of Messina Catalan Institute of Oncology Hospital Germans Trias i Pujol Molecular Oncology Research (MORe) Foundation Germans Trias i Pujol Health Sciences Institute and Hospital

Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

关键词： Lung cancer immunotherapy immune checkpoint program death-ligand 1 (PD -L 1) program death- 1 (PD - i)

Advances in immunotherapy for treatment of lung cancer

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Cancer Biology & Medicine 2015年第3期12卷 209-222页

作者： Jean G.Bustamante Alvarez María González-Cao Niki Karachaliou mariacarmela santarpia Santiago Viteri Cristina Teixidó Rafael Rosell Albert Einstein Medical Center Translational Cancer Research Unit Instituto Oncológico Dr RosellQuirón Dexeus University Hospital Medical Oncology Unit Human Pathology Department University of Messina Pangaea Biotech S.L Cancer Biology & Precision Medicine Program Catalan Institute of Oncology Germans Trias i Pujol Health Sciences Institute and Hospital Campus Can Ruti Fundación Molecular Oncology Research

Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.

关键词： Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibitors lung cancer programmed celldeath protein ligand-1 (PD-L1) programmed cell death protein i (PD-1)