[摘 要] 嵌合抗原受体自然杀伤细胞（CAR-NK细胞）疗法作为一种新兴的细胞免疫治疗策略，凭借其高安全性和“现货化”制备的独特优势，展现出比CAR-T细胞疗法更为广阔的临床应用潜力。本文深入论述了CAR-NK细胞的抗肿瘤机制，详细剖析了其靶向识别机制、固有杀伤活性，以及通过特异性受体优化以增强其在肿瘤微环境中的适应能力的最新进展。对CAR-NK细胞的多种细胞来源，包括外周血、脐带血、诱导多能干细胞（iPSC）及NK-92细胞等的优势与挑战进行了深入讨论，并总结了其在肿瘤免疫微环境中面临的持久性不足、免疫抑制，以及抗原异质性等主要瓶颈，提出了CAR-NK细胞治疗实体瘤的优势、局限性及未来发展与临床应用的方向。

In 2023,numerous theoretical advancements and technological breakthroughs have been achieved in the field of immunology research.In this article,we summarized representative research achievements in the field of immunology both domestically and internationally in 2023,and discussed the challenges and opportunities for future research.

Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 10⁶ BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.

Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.

RNA结合蛋白（RBP）由于其独特的生物学功能，目前已经成为肿瘤生物治疗相关靶点筛选的宠儿，很可能为肿瘤生物治疗带来新的机遇。RBP能调控肿瘤细胞及肿瘤微环境免疫细胞和间质细胞的DNA-RNA-蛋白质相互作用网络，进而广泛影响肿瘤发生发展、抗肿瘤免疫应答及肿瘤免疫逃逸过程，目前RBP相关肿瘤生物治疗的研发，主要聚焦在治疗性疫苗、免疫细胞治疗、表观调控治疗等方面，部分研发成果已处于临床试验阶段。随着新理论、新技术的发展以及研究模式的创新，靶向RBP的治疗逐渐摆脱了既往靶向难、疗效欠佳的困局，迎来了新的机遇，通过改良精准靶向和优化组合用药等新策略，为肿瘤生物治疗注入了新的活力，对精准个体化医疗的发展具有重要意义。

With the development of new technology and the innovation of research mode, tumor immunological research has achieved rapid development, and tumor immunotherapy has also shown remarkable clinical efficacy, jointly promoting the improvement of tumor immunology from mechanism research to clinical transformation and from single discipline to multi-disciplinary integration. However, multiple challenges still exist in tumor immunological research, such as the animal model replication for clinical tumor study, the complexity of tumor intrinsic regulation and its relationship with host microenvironment, and the screening of immunotherapy targets and the prediction of treatment effect. These problems limit the further development and application of tumor immunology, but also bring research opportunities to basic and clinical immunology researchers. Therefore, this review summarizes the research status and challenges as well as looks into the future of tumor immunity and immunotherapy in five aspects: the change of research model,the innovation of mechanism, the exploration of research objects, the screening and evaluation of therapeutic targets, as well as the application and innovation of new technologies.

TET2, a member of ten-eleven translocation (TET) family as α-ketoglutarate- and Fe

长链非编码RNA（lncRNA）是一类长度大于200 nt、且不编码的RNA。lncRNA已被证明与人类疾病紧密相关，尤其 是肿瘤发生发展。研究表明，肿瘤中一些异常表达的lncRNA可以通过不同的信号通路， 如Wnt/β-catenin信号通路，促进肿瘤进 展过程。在不同肿瘤组织中具有特异性表达特征的lncRNA与Wnt/β-catenin信号通路之间的相互作用显示出其作为新的生物标 志物和治疗靶点的潜能。本文就Wnt/β-catenin信号通路相关lncRNA通过调控Wnt/β-catenin信号转导，影响不同肿瘤类型发生 发展的作用进行综述。本文结果或可为临床肿瘤诊断和治疗提供新的思路。

Polycomb chromobox (CBX) proteins regulate gene transcription by maintaining chromatin states, which guide a variety of biological processes. Now, epigenetic regulation of innate immune response is an emerging field. However, the role of CBX proteins in innate immunity remains unclear. We confirmed that the expression of CBX family proteins, especially Cbx2, was decreased in macrophages upon viral infection, and then we investigated the role of Cbx2 in the antiviral immune response. Silencing or knockdown of Cbx2 in macrophages inhibited virus-induced production of IFN-β. Furthermore, heterozygous Cbx2 knockout were susceptible to VSV challenge. Mechanistically, Cbx2 binds to and recruits Jmjd3 to the Ifnb promoter, leading to demethylation of H3K27me3 and increased transcription of IFN-β. Together, our study reveals a non-traditional function of a Cbx protein and adds new insight into the epigenetic regulation of antiviral innate immunity.

Objective: To investigate the expression of ECT2 (epithelial Transforming sequence 2) gene in human pancreatic ductal adenocarcinoma (PDAC) and its effect on the proliferation and apoptosis of pancreatic cancer cells. Methods: Carcinoma tissues and corresponding para-carcinoma tissues from 35 PDAC patients at Changhai Hospital Affiliated to Naval Medical University from July 2018 to March 2019 were collected for this study. The differentially expressed genes in pancreatic cancer were screened out by using Gene Expression Omnibus (GEO) Database. Then, the related gene expression in PDAC and its relation with patients’survival were analyzed by The Cancer Genome Atlas (TCGA) database. QPCR and immunohistochemistry were used to verify the mRNAand protein expressions of ECT2 in human PDAC samples. To explore the effect of ECT2 on the biological behaviors of pancreatic cancer cells, si-RNA was used to silence the ECT2 gene in pancreatic cancer PANC-1 cells, and CCK-8 proliferation assay and Flow cytometry were used to detect the proliferation and apoptosis rate of PANC-1 cells after ECT2 silence. Finally, the expressions of apoptosis-related proteins were detected by WB. Results: The differentially expressed gene-ECT2, was screened out by analyzing the gene expression profiles of human pancreatic cancer in GEO database. TCGA database analysis showed that ECT2 was highly expressed in pancreatic cancer tissues (t=4.005, P<0.05) and significantly correlated with patients’survival (P< 0.01). Moreover, it is also verified that ECT2 was highly expressed in PDAC tissues at mRNA (1.01±0.06 vs 4.25±0.12; t=24.09， P<0.01) and protein level. After ECT2 silence in PANC-1 cells, the proliferation rate was decreased (P<0.01), while the Tamoxifeninduced apoptosis rate was increased (P<0.01), and the expressions of apoptosis-related proteins (BAX and Bcl-2) were also affected. Conclusion: ECT2 is highly expressed in human pancreatic ductal adenocarcinoma and is related with patients’survival. ECT2 promotes the proliferation and apoptosis resistance of pancreatic cancer cells, providing the basis for exploring ECT2 as a new target for the prognostic judgment and treatment of pancreatic cancer.