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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 teixid. 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 teixid. 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)

Erratum to Assays for predicting and monitoring responses to lung cancer immunotherapy

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Cancer Biology & Medicine 2015年第3期12卷 259-259页

作者： cristina teixid. Niki Karachaliou Maria González-Cao Daniela Morales-Espinosa Rafael Rosell Pangaea Biotech Quirón Dexeus University Hospital Dr. Rosell Oncology Institute Quirón Dexeus University Hospital Cancer Biology and Precision Medicine Program Catalan Institute of OncologyHospital Germans Trias i Pujol

In the published article1,one error appeared on page *** has not yet received FDA approval for NSCLC *** October 2014 pembrolizumab received FDA breakthrough therapy designation for lung cancer treatment supported by ... 详细信息

关键词： lung Erratum to Assays for predicting and monitoring responses to lung cancer immunotherapy

IHC、FISH和RT-PCR检测对EML4-ALK重排的一致性

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临床与病理杂志 2015年第2期35卷 189-193页

作者： cristina teixid. Niki Karachaliou Vicente Peg Ana Gimenez-Capitan Rafael Rosell 魏建国许春伟张博 Pangaea Biotech Quirón Dexeus University Institute Dr Rosell Oncology Institute Quirón Dexeus University Institute Catalan Institute of Oncology Hospital Germans Triasi Pujol 浙江省绍兴市人民医院病理科浙江绍兴312000 解放军307医院病理科北京100071

棘皮动物微管结合蛋白-间变性淋巴瘤激酶（echinoderm microtubule-associated prote i n-l ike4-anaplastic lymphoma kinase,EML4-ALK）在肺癌中已成为第二个最重要的驱动致癌基因,在4%-6%的肺腺癌中EML4-ALK已经成为第一个可以靶向治疗的融合基因位点。伴随着ALK分离探针荧光原位杂交（fluorescent in situ hybridization,FISH）试剂盒的上市,克唑替尼已经被批准治疗ALK阳性的进展期非小细胞肺癌（non-small cell lung cancer,NSCLC）。然而,一种靶向药物的成功主要取决于一种敏感且特异的筛选实验方法来检测分子药物作用的靶点。以作者的经验看,用RTPCR来检测EML4-ALK,比用FISH和免疫组化（immunohistochemistry,IHC）方法更敏感,结果更可靠。尽管通过FISH检测ALK已经经过大量的临床实验验证,然而该方法在技术层面仍存在许多具有挑战性的问题,而通过IHC和RT-PCR方法检测ALK仍需要临床进一步的探索。

关键词：间变性淋巴瘤激酶(ALK) 荧光原位杂交(FISH) 免疫组化(IHC) 非小细胞肺癌(NSCLC) 逆转录聚合酶链反应(RT-PCR)