Immune checkpoint inhibitor (ICI) has become one of the important therapeutic strategies for the patients with advanced non-small cell lung cancer (NSCLC). The latest clinical studies have shown that immunotherapy can bring more survival benefits to patients with early lung cancer and operable patients with locally advanced lung cancer. However, the strategies of neoadjuvant immunotherapy, the timing of operation, the evaluation system of curative effect, predictive markers and other problems still need to be explored in the clinical practice of large samples. This paper reviews the progress of neoadjuvant immunotherapy in NSCLC.

Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.
Humans ; Small Cell Lung Carcinoma/genetics* ; Lung Neoplasms/genetics* ; Prognosis ; Genomics ; Phenotype ; Tumor Microenvironment

Objective To investigate the efficacy and safety of surgical treatment for internal carotid artery atheromatous pseudo-occlusion (APO).Methods Clinical data of patients with carotid artery stenosis treated by carotid endarterectomy from Dec.,2011 to Jun.,2016 in Zhongshan Hospital Affiliated to Fudan University were analyzed retrospectively.Carotid endarterectomy were performed in 32 patients with pseudo-occlusion of the internal carotid artery (APO group).And 124 patients with traditional severe stenosis (70％-99％) served as control group.Perioperative major and minor complications,recurrence rate of ipsilateral ischemic stroke,restenosisrate and mortality in follow-up were compared between the two groups.Results Perioperative major complications:one patient (3.1 ％) developed myocardial infarction in the APO group,no ischemic stroke,cerebral hemorrhage and death cases;2 (1.4％) ischemic stroke cases,6 (4.2％) myocardial infarction cases and 1 (0.7％)death case was found in control group.Perioperative minor complications:1 (3.1％) incision bleeding case,2 (6.3％) pulmonary infection cases,2 (6.3％) cerebral hyperperfusion syndrome cases were found in APO group;3 (2.1％) incision bleeding cases,2 (1.4％) incision infection cases,4 (2.8％)pulmonary infection cases,2 (1.4％) cranial nerve injury cases,2 (1.4％) cerebral hyperperfusion syndrome cases were found in control group.Patients were followed up for 6-60 months,with mean follow-up period of (35.3 ± 17.5) months.During follow-up,1 (3.1％) ipsilateral ischemic stroke recurrence case,4 (12.5％) restenosis cases,and 3 (9.4％) death cases were found in the APO group.And 8 (5.6％) ipsilateral ischemic stroke recurrence cases,9 (6.3％) restenosis cases,8 (5.6％)death cases were found in control group.There were no significant differences in perioperative major and minor complications,recurrence rate of ipsilateral ischemic stroke,restenosis rate and mortality between the two groups.Conclusions Surgical treatment for atheromatous pseudo-occlusion of the internal carotid artery is safe and effective.Perioperative and follow-up results are satisfactory.

With the advent of the times of immunotherapy and the emergence of a variety of unconventional response patterns such as delayed response and pseudo-progressive disease,a variety of immune-related efficacy evaluation criteria such as immune-related response criteria,immune-related response evaluation criteria in solid tumor and immune response evaluation criteria in solid tumor have been proposed successively.The evaluation principles and judgment results of these criteria are distinctly different from the traditional response evaluation criteria.In particular,the newly proposed immune response evaluation criteria in solid tumor introduces two new concepts of unconfirmed progressive disease and confirmed progressive disease and provides a new response evaluation model for solid tumors,which is expected to provide solutions to some of the most urgent clinical problems under the times of cancer immunotherapy.

Precision detection techniques have promoted the development of individualized diagnosis and treatment of tumors in the era of precision medicine. At the same time, clinical demands of precision treatments have further driven the development and application of precision detection techniques. In recent years, precision medical detection techniques realized rapid transformations from low-throughput to high-throughput genomic sequencing, from tissue biopsies to liquid biopsies, and from multicell promiscuous detection to single cell precision sequencing. All these changes have promoted the emergence and development of new technologies, new targets, and new drugs in the era of precision oncology medicine. In the future, multi-dimensional combined detection could help to improve the accuracy of precision medicine; ctDNA methylation detection analysis could broaden the research field of precision medicine; and the transformation of clinical trial design could also contribute to promote the in-depth development of precision medicine.

近年来，免疫检查点抑制剂在肺癌治疗中取得突破性进展，正迅速改变着肺癌的治疗模式，也标志着免疫治疗2.0时 代的到来。新的肿瘤治疗模式对精准医学提出更高要求，对程序性死亡受体1（programmed death 1, PD-1） /程序性死亡配体1 （programmed death ligand 1, PD-L1）抑制剂预后生物标志物也在不断地探索之中，主要包括以下几个方面：PD-L1表达水平、肿瘤 基因组异质性与肿瘤新抗原、 T细胞特点、肿瘤微环境以及机体整体状态等。本文将针对目前PD-1/PD-L1抑制剂在肺癌免疫治 疗中的潜在生物标志物最新临床研究进展及其研究前景进行综述。

Epidermal growth factor receptor ( EGFR ) mutations are common oncogenic driver mutations in patients with non-small cell lung cancer (NSCLC). The application of EGFR-tyrosine kinase inhibitors (TKIs) is beneficial for patients with advanced and early-stage NSCLC. With the development of next-generation sequencing technology, numerous patients have been found to have more than one genetic mutation in addition to a single EGFR mutation; however, the efficacy of conventional EGFR-TKIs and the optimal treatments for such patients remain largely unknown. Thus, we review the incidence, prognosis, and current treatment regimens of EGFR compound mutations and EGFR concomitant mutations to provide treatment recommendations and guidance for patients with these mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/pharmacology* ; Mutation/genetics* ; ErbB Receptors

Immune checkpoint signaling pathway mediates tumor immune escape through various mechanisms. In recent years, studies on immune checkpoint inhibitors have made great breakthroughs in various tumors. However, characteristics of the tumor cells, abnormal presentation of the antigens, functional gene mutations, tumor immune microenvironment, internal environment of patients and metabolic factors can all lead to primary or secondary resistance to immunotherapy. The exploration of the molecular mechanism and response strategy of immunotherapy is the key to further expand the beneficial population treated by immune checkpoint inhibitors and realize the accurate treatment.

[Abstract] In recent years, investigation on immune checkpoint inhibitors has made exciting progress in anti-tumor therapy. Through continuous exploration, there is a deeper understanding of intermolecular interaction patterns among PD-L1, PD-1, CD80, CTLA-4, etc. In addition to classically acting as a T cell inhibitory receptor, PD-L1 was found to be co-expressed with PD-1 or CD80 on the same cell and play a positive immunoregulatory function through cis-interaction, significantly affecting the interaction network between tumor cells and immune cells and the efficacy of immunotherapy, and bringing new changes to the understanding of the mechanisms of cancer immunotherapy. This review provides an in-depth analysis of the cis-PD-L1/PD-1 and cis-PD-L1/CD80 pathways and their interactions with a complex network of CTLA-4 and CD28 molecules, finally outlines the effects of blocking this cis-interaction pathway on T cell signaling, cytotoxic function, and the efficacy of anti-tumor immunotherapy.

[Abstract] The research on immune checkpoint has made breakthrough progress in recent years. The PD-1/PD-L1 signaling pathway is closely related to the immune escape mechanism, and their inhibitors have also made great success in lung cancer. From Checkmate017, Checkmate-057 to KEYNOTE-010 and OAK studies, PD-1/PD-L1 inhibitors have gradually established their position as standard treatment for the advanced NSCLC patients after chemotherapy failed. PD-1/PD-L1 inhibitors can be combined with other cancer treatment methods, including radiotherapy, chemotherapy, targeted therapy and other immunotherapies, whichhave synergistic effects in the treatment of lung cancer, thus improving the efficacy. Immune checkpoint inhibitors bring changes in the treatment patterns of lung cancer, but also to the traditional efficacy evaluation model,as wellas reaction to the treatment-related adverse. In addition, the development of immune check point inhibitors has effectively promoted the progress of precision medicine.