Platelets: an emerging target for the diagnosis and therapy of cancer / 中国肿瘤生物治疗杂志

@#[摘 要] 血小板是肿瘤发生发展过程中的重要参与者，能够通过构建炎性微环境、促进血管生成和介导肿瘤免疫逃逸，直接或间接地影响肿瘤生长和转移进程。随着肿瘤微环境的动态变化，血小板的数量、体积和分子组学也发生相应改变，提示血小板相关的生物标志物具有反映肿瘤负荷演变的巨大潜力。基于血小板对肿瘤发生发展的促进效应，血小板被视为肿瘤生物治疗的重要靶点。靶向抑制血小板功能可以显著控制肿瘤的发生发展并改善患者的预后。此外，血小板对肿瘤组织具有较强的亲和能力。应用靶向血小板或血小板功能模拟的思路研发抗肿瘤靶向制剂以有效地增加纳米药物的肿瘤靶向性和生物相容性，是提高肿瘤靶向治疗效率的新兴策略。本文聚焦于血小板与肿瘤之间的复杂相互作用，在总结作用机制的基础上，对血小板相关的肿瘤标志物和抗肿瘤靶向治疗进行了重点阐述。

Mechanisms of tumorigenesis and therapeutic strategies based on gut microorganisms / 中国肿瘤生物治疗杂志

@#[摘 要] 肠道微生物是存在于人体内的庞大生态系统，它与机体形成一个相互关联的共存体。近年来得益于分子生物技术的蓬勃发展，肠道微生物组学研究表明，肠道微生物在很大程度上左右了肿瘤的发生与发展，除了微生物本身的直接作用之外，由它们引起的宿主炎症免疫系统、代谢功能方面的改变也间接发挥了重要作用，而这些变化对于后续抗肿瘤治疗也产生一定影响。基于肠道微生物的重要作用，在此基础上开发出来的微生态制剂在抗肿瘤治疗中的临床应用价值也逐渐显现，可为今后的抗肿瘤治疗提供辅助作用。本文从肠道微生物的地位、肠道微生物影响肿瘤发展的机制和对抗肿瘤治疗的影响，以及肠道微生物的临床应用等四个方面展开论述，为基于肠道微生物的抗肿瘤制剂技术的研发和临床应用提供新的思路和启示。

Immune checkpoint inhibitor-related adverse events: New exploration, new challenges / 中国肿瘤生物治疗杂志

@#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。

Cis-interaction network of PD-L1 and its impact on anti-cancer immunotherapy / 中国肿瘤生物治疗杂志

@#[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.

Genetic counseling and precise diagnosis and treatment strategies for lung cancer / 中国肿瘤生物治疗杂志

@#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.

Prognosis related factors in breast cancer patients with bone metastasis / 中国肿瘤生物治疗杂志

乳腺癌，骨转移，预后 @#乳腺癌是世界范围内女性最常见的恶性肿瘤，高达75%的患者最终会发生骨转移。骨转移发生风险与肿瘤分子分 型、组织病理和患者生理阶段等密切相关，骨转移合并其他部位转移、发生骨相关事件、骨转移灶的特点等都可影响患者的预后。 目前临床广泛应用的骨转移治疗方法包括全身应用抗肿瘤药物和骨改良药物、局部行骨转移灶放疗和骨转移灶手术。除抗肿瘤 药物外的其他治疗手段都有望改善患者预后。近年来发展的骨转移治疗新手段，如对乳腺癌原发灶的处理、放射性物质镭、骨转 移关键信号分子抑制剂和某些新技术应用在提高患者生存方面都有良好的前景。本文就乳腺癌骨转移患者的预后相关因素作 简要综述。

Development status and clinical applications of precision detection technology in the times of precision oncology / 中国肿瘤生物治疗杂志

@#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.

Research progress on Lynch syndrome / 中国肿瘤生物治疗杂志

@#Lynch综合征（Lynch syndrome，LS）是一种常染色体显性遗传病，是由于几种DNA错配修复（mismatch repair，MMR） 基因（MLH1、MSH2、MSH6、PMS2）中的一种出现种系突变，或由于EPCAM基因缺失导致MSH2表达丢失引起。LS是遗传性结 直肠癌（colorectal cancer，CRC）最常见的原因，其特征为患CRC和子宫内膜癌（endometrial cancer，EC）的风险显著增加，且存在 发生其他几种恶性肿瘤的风险。对于LS 的诊断，目前几种临床病理学标准（如阿姆斯特丹标准等）已被用于识别存在Lynch综合 征风险的个体。然而，这些标准的敏感性及特异性有限，仍有赖于临床医生对LS的警惕并关注其家族史。伴有MMR基因变异 的LS相关肿瘤通常具有微卫星高度不稳定的特征，由于移码突变新抗原的存在，可以激发强大而持久的免疫反应和肿瘤浸润淋 巴细胞浸润，所以对于LS患者，免疫检查点抑制剂将会是一种很有前景的治疗方法。由于LS是一种基因遗传病， 与DNA错配修 复缺陷具有独特关系，对其的充分理解对相关肿瘤的诊断、预防和治疗具有重要的临床意义。

Advances in immunotherapy combined with chemotherapy in the treatment of gastric cancer / 中国肿瘤生物治疗杂志

@#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。

Mechanism of tumor immune escape and treatment strategy / 中国肿瘤生物治疗杂志

@# 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。

Immunotherapy for lung cancer: new era, new thinking / 中国肿瘤生物治疗杂志

@# 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.

Research progress on immunotherapy for breast cancer / 中国肿瘤生物治疗杂志

@# 乳腺癌是中国女性最常见的恶性肿瘤，传统治疗方法存在一定副作用，而免疫治疗为攻克乳腺癌提供了新途径，尤以 晚期乳腺癌及三阴性乳腺癌（triple-negative breast cancer, TNBC）患者的PD-1/PD-L1抑制剂治疗最具发展前景。随着乳腺癌免疫 治疗相关临床试验的开展， 以HER2/nue疫苗、MUC-1疫苗等为代表的肿瘤疫苗已观察到可以改善患者的无病生存期（DFS）和总 生存期（OS）。曲妥珠单抗、帕妥珠单抗、T-DM1、MM-111等单克隆抗体也显示出较好疗效，CIK、TIL、CAR-T等过继性细胞治疗 具有较强的肿瘤杀伤能力且安全性良好，而抗PD-1/PD-L1抗体、 抗CTLA-4抗体、 抗LAG-3抗体等免疫负调控抑制剂能够抑制肿 瘤逃逸，为乳腺癌的治疗提供了新策略，这些突破性的成果推动了乳腺癌治疗实现“个体化”的进程。

Progress in clinical researches of immunotherapy for lung cancer targeting PD-1/ PD-L1 / 中国肿瘤生物治疗杂志

@#[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.

Advanced research of immune-related response evaluation criteria in solid tumors / 中国肿瘤生物治疗杂志

@# 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.

Research progress on PD-1 / PD-L1 inhibitor-based immunotherapy predictive marker in lung cancer / 中国肿瘤生物治疗杂志

@#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。

Gaining a comprehensive understanding of pruritus.

Pruritus is a common symptom associated with many dermatoses, systemic abnormalities, and psychiatric / psychosomatic diseases. Additionally, pruritus is one of the most intractable symptoms due to its complex pathogenesis involving an increasing number of mediators and receptors, undefined neurophysiologic pathways, unclear cerebral processing, and psychophysiology interaction. Clinically, the first challenge of dermatologists is how to get general and interdisciplinary vision of pruritus and to preliminarily figure it out whether there might be underlying systemic or psychosocial disorders. The second challenge is to select efficient individual tailored anti-pruritic treatment, which includes targeted drugs and cognitive-behavioral therapy.