Discovery of highly immunogenic spleen-resident FCGR3^(+)CD103^(+)cDC1s differentiated by IL-33-primed ST2^(+)basophils

Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103^(+)cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103^(+)cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3^(+)CD103^(+)cDC1s,which were found to be differentiated from DC precursors by bystander ST2+immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2^(+)basophils play a crucial role in the development of FCGR3^(+)CD103^(+)cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3^(+)CD103^(+)cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.

外周血T细胞亚群和ST2L在NSCLC抗PD-1治疗中的变化

目的:探讨晚期非小细胞肺癌(NS C LC)患者抗P D-1治疗前后C D4^(+)、C D8^(+)、C D4^(+)/C D8^(+)比值、ST2L水平变化。方法:选取2020年1月—2022年1月江苏大学附属武进医院行抗P D-1治疗的晚期非小细胞肺癌患者30例为肺癌组,选取同期30名体检健康者作为对照组。所有患者在第1次抗PD-1治疗前及抗PD-1治疗2、4周期后,空腹抽取外周血5 mL,SemiBio细胞免疫芯片检测两组患者免疫治疗前及治疗2、4周期后患者外周血CD4^(+)、CD8^(+)计数,ELISA检测ST2L。通过生物信息学方法分析ST2与CD4^(+)T细胞、CD8^(+)T细胞的相关性;通过ssGSEA(single sample GSEA)方法,分析每个免疫组ST2的表达水平。结果:生信分析ST2与CD4^(+)T细胞、CD8^(+)T细胞浸润、免疫治疗疗效相关。与对照组相比,肺癌组抗PD-1治疗前后外周血CD4^(+)细胞水平、CD4^(+)/CD8^(+)均低于对照组,CD8^(+)细胞水平高于对照组,差异有统计学意义(P<0.05);肺癌组抗PD-1治疗后,外周血CD4^(+)细胞水平、CD4^(+)/CD8^(+)较治疗前升高,差异有统计学意义(P<0.05),治疗后C D8^(+)细胞水平较治疗前降低,但差异无统计学意义(P>0.05);与对照组相比,肺癌组抗P D-1治疗前后外周血低表达ST2L,差异有统计学意义(P<0.05)。治疗后,抗PD-1外周血ST2L表达量较治疗前明显增多,差异有统计学意义(P<0.05)。结论:晚期非小细胞肺癌患者存在免疫抑制,治疗后抗P D-1免疫功能显著改善,外周血C D4、CD4^(+)/CD8^(+)比值、ST2L表达可能成为抗PD-1治疗的疗效预测标记物。

一种NR-V2X层三信息的物理层解析方案

为了适应NR-V2X中物理层与RRC层技术的改进,基于3GPP的R16协议,提出了一种完整的NR-V2X层三信息的物理层解析方案。首先,通过本地同步信号与接收信号的相关,检测出主辅同步信号的时频位置;然后根据从同步信号中获得的参数集信息解析PSBCH,实现与发送UE的帧同步;接下来根据协议中对PSCCH和PSSCH资源分配的描述,提取出PSCCH和PSSCH,分别解析获得1^(st) stage SCI和2^(nd) stage SCI。借鉴了已经成熟的NR层三解析方案,针对V2X的特性做了相应的改动,降低了NRV2X物理层算法的设计复杂度,减少了NR-V2X终端接收部分的物理层开发周期。