In recent years, immune checkpoint inhibitors have been continuously researched and developed, and gradually expanded in clinical practice, rapidly changing the treatment mode of lung cancer. At present, a number of immunotherapeutic drugs are also actively developed in China and gradually applied to clinical research, indicating that China has entered a new era of immunotherapy. However, with the continuous expansion of clinical research and the continuous accumulation of experimental data, it also brings us many new challenges and new thinking. This article mainly analyzes the development status and challenges of immunotherapy for lung cancer in the aspects of breakthroughs in treatment modes, special populations excluded from clinical immunotherapy trials, response evaluation, treatment-related adverse events and predictive biomarkers.

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.

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。

肿瘤免疫逃逸是肿瘤发生发展的十大特征之一，针对免疫逃逸环节的免疫疗法近年来取得了显著的成功。免疫疗法涉 及多个因素和环节，与肿瘤细胞自身和肿瘤微环境的改变均有相关且机制复杂，目前在临床实践过程中仍面临着不小的挑战。 本文从3个方面介绍了肿瘤免疫逃逸的机制，包括肿瘤自身的改变、肿瘤诱导微环境的改变以及肿瘤微环境促进肿瘤的发展。同 时针对这些机制，将目前的治疗策略进行了梳理，包括免疫检查点抑制剂、CAR-T疗法以及免疫细胞疗法等的困境与进展，旨在 为肿瘤免疫治疗的下一步发展理清思路。

胃癌患者具有相对较高的突变负荷、新抗原基数和肿瘤浸润淋巴细胞，表明其对免疫治疗可能具有潜在应答性，但多 项研究显示，免疫检查点程序性死亡受体1（programmed death protein1, PD-1）抑制剂单药治疗应答率仅为10%~26%。近期，人们 对化疗对机体免疫系统的影响进行了深入探究，证实化疗药物可通过不同免疫调节机制对肿瘤免疫应答产生影响。多项研究显 示，免疫治疗联合化疗药物在提高患者客观缓解率（ORR）和延长生存期方面具有一定成效，联合方案逐渐成为目前晚期胃癌研 究的热点。本文主要阐述化疗药物对肿瘤免疫应答的影响、免疫治疗联合化疗在晚期胃癌中的应用及预测疗效的生物标记物的 进展，以期为胃癌的临床治疗提供参考。

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，通过增强机体免疫系统对肿瘤细胞的杀伤作用，免疫检查点抑制剂（immune checkpoint inhibitor，ICI）在抗 肿瘤治疗中的应用获得了显著的临床疗效。然而，多项证据表明，免疫治疗激活免疫系统的同时可导致独特的免疫相关不良反 应（immune-related adverse events，irAEs），影响免疫治疗的疗效或需要中止治疗。近几年，随着 ICI 治疗临床试验的广泛开展， irAEs 的发生情况、毒性谱及其有效管理手段的开发越来越得到临床医生的关注。常见的 irAEs 包括皮炎和甲状腺炎等，而不 同种类免疫检查点抑制剂、不同治疗剂量或组合疗法，均可导致不同的 irAEs 毒性谱，同一免疫检查点抑制剂作用于不同肿瘤 所致的毒副反应谱亦有不同。目前认为，irAEs 的发生与机体自身免疫系统功能的改变相关，包括机体免疫系统过度激活、自身 免疫耐受性的打破等，但其具体机制仍不十分清楚。本文结合近年来在 ICI 治疗中 irAEs 相关分子机制和预测标志物的关键理 论和认识方面取得的诸多新进展，对 irAEs 的发生特点和分子机制进行总结，并就其预测性标志物开发、irAEs 管理原则改进和 治疗新探索进行述评。

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

In recent years, therapy of immune checkpoint inhibitors have developed rapidly and made breakthrough, becoming the first-line treatment for many types of advanced cancer. However, due to its particular mode in activating the anti-tumor immune system, a variety of unconventional response patterns have emerged, such as delayed response and pseudoprogression, which have challenged the traditional response evaluation criteria and encouraged people to continuously explore new criteria for evaluating the unconventional response patterns under immunotherapy. This article mainly reviews the process of exploration, advanced research,as well as similarities and differencesamongvarious immune-related efficacy evaluation criteria, and finally prospects the current challenges and future trends.

Environmental factors are important risk factor for lung cancer. Smokers are 20 times more likely to develop lung cancer than non-smokers. However, less than 20% of smokers develop lung cancer. In recent years, many studies have shown genetic polymor‐phism plays an important role in the development of lung cancer, mainly involving single nucleotide polymorphisms and rare highexogenous mutations. The in-depth research of the gene polymorphism will be beneficial to the screen of susceptible genes in lung cancer and genetically high-risk population, providing genetic counseling and evidence for clinically precise diagnosis and treatment. This article mainly summarizes the contents regarding genetic susceptibility of lung cancer and high-risk population screening, early diagnosis of lung cancer as well as precise medication of advanced lung cancer.