Colorectal cancer （CRC） ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years， there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence， and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway， the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies， and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes， such as proliferation， differentiation， and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine （TCM） can inhibit the proliferation， invasion， migration， and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore， this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy， thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years， research results have been updated rapidly， and previous literature summaries have failed to incorporate the latest findings， creating obstacles to accessing current literature. Therefore， this article supplements and summarizes information from the definition of the JAK/STAT pathway， association of this pathway with CRC， and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.

[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。

[摘 要] 嵌合抗原受体基因修饰T细胞（CAR-T细胞）疗法是一种肿瘤免疫治疗方法：来自人体的T细胞在体外经遗传学修饰、表达特异性嵌合抗原受体（CAR），然后将其回输入患者体内，用于靶向识别和消除肿瘤细胞。尽管CAR-T细胞疗法在血液系统肿瘤治疗中取得了较为显著的成功，其在实体瘤治疗中仍面临障碍。细胞因子释放综合征（CRS）等免疫相关不良反应（irAE）制约了CAR-T细胞的安全应用，肿瘤相关抗原（TAA）的异质性限制了单一CAR-T细胞的广谱适用性，也制约了其通用型开发。鉴于此，要使CAR-T细胞疗法在实体瘤临床治疗中得到应用，还需开展进一步的改良与提升研究。本文围绕实体瘤中CAR-T细胞疗法，从“CAR基因修饰策略”、“通用免疫受体的再靶向策略”及“抗原通用性‘赋靶’策略”三个方面对CAR-T细胞领域中为提高安全性和通用性所进行的探索进行述评，系统剖析各策略的研究路径、优势及局限性，并展望未来发展方向。通过综述CAR-T细胞安全性和普适性设计策略的进展，本文旨在为实体瘤的CAR-T细胞疗法研发提供创新思路。

Tumor immunotherapy has achieved breakthroughs in the treatment of malignant tumors by activating the host immune system’s antitumor response mechanism. Among various strategies, Toll-like receptor (TLR) agonists have garnered substantial attention due to their unique immunomodulatory capabilities. This work reviews the research progress on the combination of TLR agonists with radiotherapy in tumor immunotherapy, focusing on the clinical translational potential of intratumoral injection strategies. Clinical studies have shown that the in-situ injection of TLR agonists in combination with radiotherapy can effectively suppress primary and metastatic lesions by inducing immunogenic cell death, releasing tumor antigens, activating local immune responses, and triggering abscopal effects. Moreover, novel extended-release formulations and “endogenous vaccine” designs further enhance the safety and durability of treatment. Despite several challenges such as tumor microenvironment suppression and dose optimization, TLR agonists hold promise for the treatment of “cold” tumors lacking innate immunity through combinations with immune checkpoint inhibitors, nanodelivery technologies, and precise biomarker screening.

[摘 要] 目的：基于噬菌体展示靶向锚定蛋白文库，以人白细胞抗原G（HLA-G）为靶点筛选锚定序列作为HLA-G结合蛋白（HGBP）并评价其功能。方法：利用TCGA、GTEx等数据库分析肿瘤组织中HLA-G表达与临床预后和免疫浸润的相关性。利用噬菌体展示靶向锚定蛋白文库对HLA-G胞外片段进行生物淘选并随机挑取单克隆进行测序。通过ELISA、免疫荧光染色鉴定优势噬菌体克隆的功能。利用原核体系生产纯化HGBP，通过ELISA、表面等离子共振（SPR）、免疫荧光染色法评价其亲和力及肿瘤特异性结合能力。结果：生物信息学分析发现，HLA-G在肿瘤组织中普遍呈高表达，其与临床总生存期、免疫细胞浸润水平具有相关性（P < 0.05）。5轮噬菌体文库筛选后获得优势克隆，ELISA及免疫荧光染色结果均显示，优势噬菌体对HLA-G阳性细胞结合显著强于阴性细胞（P < 0.05, P < 0.001）。经纯化生产的HGBP与HLA-G之间的亲和力可达17 nmol/L，ELISA结果显示，HGBP与HLA-G分子的结合显著（P < 0.05）；免疫荧光染色结果表明，HGBP能与HLA-G阳性细胞特异性结合（P < 0.01）。结论：经噬菌体展示文库筛选出的HGBP对HLA-G具有高亲和力，可特异性结合肿瘤细胞表达的HLA-G。

[摘 要] 过继细胞疗法在肿瘤免疫治疗领域持续革新，其中双特异性抗体武装T细胞/自然杀伤细胞（T/NK细胞）技术通过抗体靶向并桥接免疫细胞，赋予其精准靶向杀伤能力的同时突破传统技术局限，兼具制备标准化程度高、安全性可控及临床转化周期短等核心优势，在实体瘤及血液系统恶性肿瘤治疗中均呈现出突破性临床潜力。本文系统评述嵌合抗原受体基因修饰T淋巴细胞/自然杀伤细胞（CAR-T/NK细胞）、肿瘤浸润淋巴细胞（TIL）和细胞因子诱导的记忆样NK细胞（CIML NK细胞）疗法的研究进展，并重点探讨双特异性抗体武装T/NK细胞技术的作用机制、优势、临床进展及前沿趋势。

In situ tumor vaccine has become an important strategy in cancer immunotherapy owing to its ability to induce immune responses locally and overcome tumor heterogeneity. However, the abnormal structure and mechanical properties of the tumor’s physical microenvironment significantly limit the efficiency of vaccine delivery and immune efficacy. In this review, the key factors in the tumor’s physical microenvironment, including solid pressure, interstitial fluid pressure, matrix stiffness, and tissue microstructure, are systematically discussed. Their obstructive roles in immune cell infiltration, antigen presentation, and immune activation are analyzed. The potential of approaches, such as radiotherapy, anti-angiogenic therapy, extracellular matrix degradation agents, nanomaterials, and hydrogel delivery platforms, in reshaping the tumor’s physical microenvironment is explored. This review aims to offer theoretical and practical guidance for optimizing in situ vaccine strategies through the regulation of the tumor’s physical microenvironment, ultimately advancing the precision and effectiveness of cancer immunotherapy.

BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans ; Lung Neoplasms/metabolism* ; Interleukin-5/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Biomarkers ; Immunotherapy ; Disease Progression ; B7-H1 Antigen

[摘 要] 肿瘤免疫治疗是一种新兴且发展前景广阔的治疗模式。间皮素是一种细胞表面膜蛋白，通过糖基化磷脂酰肌醇锚定在细胞膜上。间皮素在多种恶性实体肿瘤及血液恶性肿瘤中呈高表达，在少数正常组织的间皮细胞中呈低表达，是一个有潜力的肿瘤免疫治疗靶点。间皮素的高表达与患者不良预后密切相关，可溶性间皮素已成为多种肿瘤的诊断性生物标志物。应用抗体药物偶联物和CAR-T细胞治疗等免疫治疗策略，针对间皮素阳性实体瘤进行转化研究并取得了初步进展。本文对间皮素的结构、体内分布、生物学功能、肿瘤细胞内信号传导机制及其作用、基于核素的靶向成像与治疗策略、抗体偶联药物和CAR-T细胞的治疗策略，以及面临的挑战进行系统阐述，为进一步探索以间皮素为靶点的免疫治疗提供新思路。

[摘 要] 免疫疗法正引领抗肿瘤治疗领域迈向新时代，其中新抗原疫苗作为免疫治疗的先锋力量，正以前所未有的速度推进其基础研究与临床试验，成果迭出，彰显出广阔的发展前景。本文聚焦于新抗原疫苗领域的最新进展，详细介绍备受瞩目的长肽疫苗与mRNA疫苗两大亮点。肽疫苗因生产高效、易规模化而受关注，虽存在降解快等限制，但纳米载体等技术可帮助其扬长避短，目前长肽疫苗在黑色素瘤、脑胶质瘤等多种实体瘤患者中均显示出不错的疗效，纳米化的短肽疫苗也在胃癌辅助治疗中展露优势。mRNA疫苗因在新冠疫情防控中应用广泛受到关注，其安全性及编码多种抗原的优势使其成为肿瘤疫苗热点，如编码多个KRAS突变的RNA疫苗在胰腺癌中展现出良好效果。且多项研究表明新抗原疫苗联合免疫检查点抑制剂或过继性细胞治疗可发挥协同作用，进一步提高疗效。文章深入剖析当前新抗原疫苗在临床转化阶段所面临的诸多挑战，并在此基础上，积极探索并讨论可能的应对策略，旨在为新抗原疫苗未来的发展方向启迪新思维，开辟新路径。