肿瘤第一线 · 学术知识传播

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AIM2和NLRP3炎症小体在辐射期间诱发IL-1介导的抗肿瘤作用

2021-11-29 姜新 姜新

炎症小体是一种胞质多蛋白复合物,是通过对病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs)的响应而形成的,在宿主防御感染和肿瘤过程中起着关键作用。

原文出处
Han C, Godfrey V, Liu Z, et al. The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation. Sci Immunol. 2021 May 7;6(59):eabc6998. doi: 10.1126/sciimmunol.(I区,IF = 17.223)


研究背景
炎症小体是一种胞质多蛋白复合物,是通过对病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs)的响应而形成的,在宿主防御感染和肿瘤过程中起着关键作用。NLRP3可以识别广泛的PAMPs和DAMPs,包括活性氧(ROS)。黑色素瘤2(AIM2)中缺失的细胞质DNA传感器是一种非NLR炎性小体形成的模式识别受体,也参与炎性小体的激活。NLRP3或AIM2通过其特定配体激活后,通过凋亡相关斑点样蛋白与caspase-1(Casp1)相互作用,形成大的多分子炎性小体复合物。这种相互作用激活Casp1,产生成熟的IL-1和IL-18。IL-1具有多种生物学功能,包括激活淋巴细胞以及将中性粒细胞聚集到局部组织。趋化因子和细胞因子的分泌在感染区域或肿瘤组织中建立了一个炎症微环境。


与许多引起促炎免疫反应的急性感染不同,肿瘤可促进慢性炎症以建立免疫抑制肿瘤微环境。值得注意的是,炎性小体在肿瘤诱导的免疫抑制和肿瘤发生中发挥作用,特别是在炎症诱导的癌症中。此外,新的证据表明,阻断炎性小体介导的IL-1信号可能有助于控制肿瘤的生长。研究表明,在Casp1敲除小鼠(Casp1−/−)中或阻断IL-1信号时,肿瘤生长较慢。放射治疗是一种广泛应用的癌症治疗方法。辐射的功效主要依赖于直接杀死肿瘤细胞以及随后引起的免疫反应。T细胞介导的抗肿瘤免疫有助于局部放疗后的肿瘤抑制。AIM2和NLRP3可导致辐射诱导的细胞死亡和组织损伤。巨噬细胞中的病毒感染可以诱导AIM2炎性小体的激活,限制cGAS-STING通路。提示炎性小体可能抑制放疗介导的抗肿瘤免疫应答。然而,作者发现,Casp1−/−小鼠的肿瘤生长速度比对照组小鼠慢,并且对放疗有抵抗性。具体来说,辐射诱导了AIM2和NLRP3炎症小体的激活,它们协同导致巨噬细胞中IL-1的产生和随后的树突状细胞(DC)的激活。DC激活导致更强的T细胞免疫反应和强大的抗肿瘤免疫。

 

研究结果
结果一、Casp1信号增强了放疗的抗肿瘤作用
考虑到炎性小体在限制cGAS-STING信号通路激活中的作用,作者假设Casp1在小鼠体内的缺失会通过刺激cGAS-STING通路的激活来限制肿瘤的生长并增强放疗作用。作者观察到MC38移植瘤在Casp1−/−小鼠中的生长速度比野生型(WT)小鼠慢(图1A)。因此,作者想知道Casp1缺乏是否对放疗诱导的肿瘤抑制起到有益的作用。为了验证这一概念,作者验证了WT或Casp1−/−小鼠照射后MC38肿瘤的生长情况。出乎意料的是,Casp1−/−小鼠的肿瘤对放疗的反应不如WT小鼠(图1B、补充材料1A)。由于肿瘤在Casp1−/−小鼠中生长更为缓慢,作者希望排除放疗的抗肿瘤作用不是由于WT和Casp1−/−小鼠之间肿瘤生长动力学改变的可能性。因此,作者在Casp1−/−小鼠中接种了两倍于WT小鼠的肿瘤细胞,保证放疗后肿瘤大小相似(补充材料1B)。与作者最初的观察相似,放疗在控制Casp1−/−小鼠移植瘤的生长方面没有效果(图1C)。作者还利用B16-OVA肿瘤评估了Casp1在放疗诱导的肿瘤抑制中的作用。结果显示未处理的B16-OVA肿瘤在WT和Casp1−/−小鼠中生长相似。然而,在Casp1−/−小鼠中,放疗并不能有效地控制B16-OVA肿瘤(图1D)。这些数据表明,Casp1表达在辐射诱导的抗肿瘤活性中发挥关键作用。



Fig. 1. Tumor growth of irradiated tumors in WT and Casp1−/− mice. (A) The tumor growth curve is shown as a measure of tumor volume in WT (n = 7) or Casp1−/− (n = 5) mice that were subcutaneously transplanted with 1 × 106 MC38. (B) The tumor growth curve is shown as a measure of tumor volume in C57BL/6/J mice (n = 5 to 6) or Casp1−/− mice (n = 6 to 7) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (C) The tumor growth curve is shown as a measure of tumor volume in C57BL/6/J mice (n = 5) that were subcutaneously transplanted with 1 × 106 MC38 cells, or in Casp1−/− mice (n = 6 to 8) that were subcutaneously transplanted with 2 × 106 MC38 cells. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (D) The tumor growth curve is shown as a measure of tumor volume in WT or Casp1−/− mice (n = 4 to 5) that were subcutaneously transplanted with 5 × 105 B16-OVA. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. Data are shown as means ± SEM and are representative of three (A to C) or two (D) independent experiments. The statistical analysis was performed by two-way ANOVA test. **P < 0.01 and ****P < 0.0001.
图1、补充材料1


结果二、辐射激活了AIM2和NLRP3炎症小体
辐射会引起DNA损伤和细胞死亡,从而增加胞质和细胞外的dsDNA。因为AIM2是在感应到dsDNA后形成炎症小体的。作者想知道放疗是否激活了肿瘤免疫微环境中的AIM2炎症小体。为了解决这个问题,作者将MC38肿瘤细胞移植到AIM2−/−小鼠中,并对肿瘤进行放射治疗。与Casp1−/−小鼠的肿瘤不同,AIM2−/−小鼠的MC38肿瘤对放疗仍然敏感(图2A)。放疗增加了ROS的产生,并将线粒体DNA释放到胞质中,诱导Ca2+和K+内流,从而激活NLRP3炎症小体。因此,作者研究了NLRP3是否在放疗引起的MC38肿瘤抑制中发挥作用,NLRP3−/−小鼠对放疗的反应情况与WT和AIM2−/−小鼠相似(图2A)。


在骨髓移植模型中,辐射能够激活AIM2和NLRP3炎症小体。基于上述结果,作者建议在体外系统中鉴定免疫细胞中AIM2和NLRP3炎症小体激活对照射肿瘤释放DAMPs的相对贡献。因此,作者将照射后的MC38肿瘤细胞与WT、Casp1−/−或AIM2−/−巨噬细胞共培养。通过ELISA测定,照射后的肿瘤细胞触发WT巨噬细胞中IL-1β的产生,但未触发Casp1−/−巨噬细胞IL-1β的产生(补充材料2A)。这表明辐射的肿瘤源性介质激活了炎性小体。与野生型巨噬细胞相比,AIM2−/−巨噬细胞部分减少了IL-1β的产生(补充材料2A)。作者还在WT和AIM2−/−巨噬细胞中使用小分子抑制剂MCC950抑制NLRP3炎症小体。MCC950进一步降低WT和AIM2−/−巨噬细胞中IL-1β的产生。这些数据表明,AIM2和NLRP3在辐射诱导的炎症小体激活和IL-1β的产生中发挥协同作用。


为了验证AIM2和NLRP3在IL-1β产生中发挥协同作用的假设,作者采用了AIM2−/−NLRP3−/−小鼠,它们的AIM2和NLRP3基因表达都有缺陷(补充材料2B、2C),并通过Western blotting进行验证(补充材料2D)。MC38肿瘤移植到AIM2−/− NLRP3−/−小鼠体内。在AIM2−/− NLRP3−/−小鼠中,肿瘤对辐射具有抗性,这表明当AIM2和NLRP3均不活跃时,辐射诱导的肿瘤生长阻滞作用将受到抑制(图2B)。为了证实AIM2和NLRP3双重缺失对辐射诱导Casp1激活的影响,作者将来自WT、Casp1−/−、NLRP3−/−、AIM2−/−和AIM2−/− NLRP3−/−小鼠的巨噬细胞与辐射处理的MC38细胞共培养,并用ELISA检测成熟IL-1β的水平,与AIM2−/− NLRP3−/−小鼠的辐射响应性一致,IL-1β的产生在双敲除组减少,而AIM2−/−或NLRP3−/−巨噬细胞仅部分减少IL-1β的产生(图2C)。因此,AIM2和NLRP3共同起到调节放疗介导的抗肿瘤活性作用。


接下来,作者研究了照射后的肿瘤细胞刺激巨噬细胞中AIM2和NLRP3炎症小体激活的机制。由于细胞分子和细胞器可以直接或通过细胞外囊泡(EV)分泌,作者想要检测EV或非EV组分是否能够激活炎症小体。因此,作者收集辐照后的MC38细胞培养液,从培养上清中纯化EV,分离无EV上清。然后将WT或炎性小体缺陷小鼠的巨噬细胞与EV或无EV上清共同孵育。照射后的MC38肿瘤细胞产生的EV显著增加了WT细胞中IL-1β的产生(补充材料2E)。在Casp1−/−和AIM2−/− NLRP3−/−巨噬细胞中未观察到IL-1β水平升高(补充材料2E)。这些数据表明,照射后肿瘤细胞来源的EV可以激活AIM2和/或NLRP3炎症小体。结果证明AIM2参与了EV诱导的IL-1β的产生,而不是NLRP3(图2D),这表明照射后的肿瘤细胞来源的EV激活了巨噬细胞中的AIM2炎症小体。相比之下,无EV上清以NLRP3依赖的方式触发IL-1β的产生(图2E)。为了进一步证实照射触发了肿瘤中外泌体的形成,作者分析了纯化囊泡中CD63和CD9的表达情况。结果表明CD63和CD9阳性外泌体的产生在照射过的MC38肿瘤细胞中更高(补充材料2F、2G、2H)。这些数据表明,照射后的肿瘤可通过EV和非EV组分触发髓系细胞中AIM2和NLRP3炎症小体的激活。


Fig. 2. Identification of the role of AIM2 and NLRP3 inflammasome to RT. (A) The tumor growth curve is shown as a measure of tumor volume in C57BL/6/J, Aim2−/− or Nlrp3−/− mice (n = 5 to 7) that were subcutaneously transplanted with 2 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (B) The tumor growth curve is shown as a measure of tumor volume in C57BL/6/J or Aim2−/−Nlrp3−/− mice (n = 5) that were respectively subcutaneously transplanted with 1 × 106 or 2 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (C) ELISA analyzing BMDM-derived IL-1 levels (n = 3). (D and E) ELISA analyzing BMDM-derived IL-1 level. The purified EVs (D) or EV-free supernatant (E) were added to the macrophage for 48-hour culturing. Then, IL-1 level in the supernatant was analyzed by ELISA (n = 3). Data are shown as means ± SEM and are representative of three (A to E) independent experiments. The statistical analysis was performed by two-way ANOVA test in (A) and (B) and by unpaired Student’s t test in (C) to (E). *P < 0.05, ***P < 0.001, and ****P < 0.0001.
图2、补充材料2


结果三、放疗诱导的抗肿瘤免疫需要宿主中的IL-1信号通路
炎症小体导致两种关键的炎症细胞因子IL-18和IL-1β的分裂。作者照射IL-18r1−/−、IL-18−/−或IL-1r1−/−小鼠中的MC38肿瘤并监测肿瘤生长。作者观察到IL-18r1−/−和IL-18−/−小鼠的肿瘤对放疗敏感(图3A、补充材料3A),而IL-1r1−/−小鼠肿瘤则对辐射有抵抗(图3B)。这些结果表明,IL-1信号通路而非IL-18信号通路参与了RT的抗肿瘤活性。由于IL1r1能够识别IL-1β和IL-1α,作者研究了在辐射介导的抗肿瘤免疫反应中发挥关键作用的细胞因子。为了解决这个问题,作者采用重组抗体在WT小鼠中阻断IL-1β,以评估辐射诱导的肿瘤衰退。结果显示IL-1β阻断不影响放疗的疗效(补充材料3B)。作者推测这种作用可能是由IL-18和IL-1β的共同作用引起的。因此,作者在IL-18r1−/−小鼠中检测了阻断IL-1β后放疗的抗肿瘤活性。出乎意料的是,阻断IL-1β并没有改变IL-18r1−/−小鼠中MC38肿瘤的辐射敏感性(图3C)。这些观察结果出乎意料,但指出IL-1r1上游细胞因子可能参与了增强放疗治疗效果的过程。AIM2和NLRP3炎症小体也调节IL-1β的产生,同时IL-1β也通过IL-1r1传递信号。因此,作者继续研究了IL-1β和IL-1α在辐射介导的肿瘤生长抑制中的协调作用。阻断IL-1β和IL-1α均不影响放疗的治疗效果,但阻断IL-1β和IL-1α可降低肿瘤的放射敏感性(图3D)。为了研究Casp1是否对IL-1β的产生也至关重要,作者随后检测了共培养系统和肿瘤组织中IL-1β的蛋白水平。Casp1−/− BM来源的巨噬细胞(BMDM)与照射后的MC38肿瘤细胞共培养时产生的IL-1β少于野生型BMDM细胞(补充材料3C)。此外,带瘤Casp1−/−小鼠放疗后血清IL-1β水平也低于WT小鼠(补充材料3D)。这些结果表明,IL-1在辐射诱导的肿瘤生长抑制中发挥了重要作用。



Fig. 3. Exploring the effect of IL-1 pathway to RT. (A) The tumor growth curve is shown as a measure of tumor volume in C57BL/6 or Il18r1−/− mice (n = 4 to 7) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (B) The tumor growth curve is shown as a measure of tumor volume in C57BL/6 (n = 4 to 5) or Il1r1−/− mice (n = 3 to 5) that were subcutaneously transplanted with 2 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (C) The tumor growth curve is shown as a measure of tumor volume in Il18r1−/− mice (n = 4 to 5) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. Then, anti–IL-1 antibody (100 g per mice) was intratumorally injected. (D) The tumor growth curve is shown as a measure of tumor volume in WT mice (n = 4 to 5) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. Then, 100 g of anti–IL-1 antibody or/and anti–IL-1 antibody were intratumorally injected. Data are shown as means ± SEM and are representative of three (A to C) and two (D) independent experiments. The statistical analysis was performed by two-way ANOVA test. **P < 0.01 and ****P < 0.0001.
图3、补充材料3


结果四、IL-1通过刺激树突状细胞引发抗肿瘤T细胞反应
接下来,作者研究了哪些免疫细胞类型参与了Casp1/IL1r1介导的放疗的抗肿瘤作用。因为IL1R1信号在T细胞激活中起关键作用。我们首先利用Cd4-Cre; IL-1r1fl/fl小鼠(T细胞中特异性丧失IL-1r1)评估了T细胞固有IL-1信号在辐射诱导的抗肿瘤免疫中的作用(补充材料4A)。出乎意料的是,T细胞中IL-1信号的丢失只是轻微地降低了MC38肿瘤对辐射的敏感性(图4A)。这表明,IL-1主要针对T细胞以外的细胞,以促进辐射的抗肿瘤作用。巨噬细胞在早期激发放疗的抗肿瘤作用中起重要作用;然而,它们也涉及建立一种免疫抑制的肿瘤免疫微环境,以支持肿瘤在放疗晚期的生长。作者在巨噬细胞中生成了IL-1r1缺乏的Lyz2-Cre; IL-1r1fl/fl小鼠(补充材料4B)。结果显示与IL-1r1fl/fl小鼠一样,Lyz2-Cre; IL-1r1fl/fl小鼠也对放射治疗有反应(图4B、4C)。这表明IL-1并不以巨噬细胞为靶点以促进放射治疗。主要的抗原提呈细胞DCs,在启动肿瘤特异性T细胞反应和放疗诱导的抗肿瘤免疫中起至关重要的作用。因此,作者构建了zDC-Cre; IL-1r1fl/fl小鼠,它们在DCs中特异性缺乏IL-1r1信号(补充材料4C)。结果显示,zDC-Cre; IL-1r1fl/fl小鼠对放疗反应不良,提示辐射诱导的DC中Casp1/IL-1信号在辐射诱导的抗肿瘤免疫应答中发挥作用(图4D)。



Fig. 4. IL-1 targets DC to enhance radiation-mediated antitumor immunity. (A) The tumor growth curve is shown as a measure of tumor volume in Cd4-Cre-;Il1r1fl/fl or Cd4-Cre+;Il1r1fl/fl mice (n = 4 to 5) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (B) The tumor growth curve is shown as a measure of tumor volume in Il1r1fl/fl mice (n = 4 to 5) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (C) The tumor growth curve is shown as a measure of tumor volume in Lyz2-Cre;Il1r1fl/fl mice (n = 7) that were subcutaneously transplanted with 1 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. (D) The tumor growth curve is shown as a measure of tumor volume in zDC-Cre;Il1r1fl/fl mice (n = 4 to 5) that were subcutaneously transplanted with 2 × 106 MC38. Tumors were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. Data are shown as means ± SEM and are representative of three (A to D) independent experiments. The statistical analysis was performed by two-way ANOVA test. **P < 0.01 and ****P < 0.0001.


CD8+ T细胞是辐射抑制肿瘤生长所必需的。DCs可通过交叉引物启动肿瘤特异性CD8+ T细胞。DC特异性IL-1信号在放疗中的重要作用,使得人们思考IL-1靶向DC是否可以调节CD8+ T细胞的功能。放疗过程中肿瘤内的CD8+ T细胞对放疗有抵抗作用,阻断放疗过程中肿瘤内CD8+ T细胞的浸润并不影响放疗的治疗效果。这表明,放疗后肿瘤中已存在的(CD8+ T细胞在放疗前存在)CD8+ T细胞,而不是新近浸润的CD8 + T细胞,可能是辐射诱导的抗肿瘤免疫的主要效应因子。因此,作者推测,在DC中IL-1信号通路是激发辐射特异性肿瘤内CD8+ T细胞所必需的。为了验证这一可能性,作者从脾细胞中分离出OVA肽SIINFEKL (OT-1)特异性CD8+ T细胞,并对其进行辐照,模拟辐照瘤内CD8+ T细胞细胞,然后,将OVA预处理的DCs与辐照后的OT1 CD8+ T细胞细胞共培养。IL-1r1−/−与野生型DCs相比,CD8+ T细胞显著减少IFN-γ和IL-2的产生(图5A、5B、补充材料5A)。IL-1β处理进一步增加了与WT共培养的CD8+ T细胞IFN-γ和IL-2的产生,但在IL-1r1−/−DCs中并未观察到这种情况(图5A、5B)。IL-1β处理也增加了CD8+ T细胞与WT共培养时的存活率,但对IL-1r1−/−DCs没有影响(图5C、补充材料5B)。为了证实这一观察结果,作者还调查了放疗后原有肿瘤CD8+ T细胞的生存情况。IL1r1信号不影响巨噬细胞和DCs的存活(补充材料5C、5D、5E)。然而,与野生型小鼠相比,IL-1r1−/−小鼠的T细胞更少(图5D、5E、补充材料5E)。总之,这些数据表明,辐射以Casp1依赖的方式刺激了AIM2和NLRP3炎症小体的激活,并促进了IL-1的产生。通过促进DC的交叉启动功能,IL-1进一步启动已有的CD8+ T细胞。



Fig. 5. IL-1 signaling in DCs contributed to the survival of preexisting CD8+ T cells after RT. (A and B) Cross-priming assay to investigate the role of IL-1 signaling in DC to the activation of CD8+ T cells. IFN-γ (A) and IL-2 (B) release was determined by CBA assay. (C) The total cells were collected and stained with annexin V and CD8 to distinguish apoptotic and live CD8+ T cells in cross-priming assay (C). (D and E) Analyzing the survival of preexisting CD8+ T cell after RT. Tumors in C57BL/6/J or Il1r1−/− mice (n = 4 to 5) were untreated (NR) or treated locally with one dose of 15-Gy (IR) radiation. To block the new infiltrated T cells, FTY720 (30 g per mouse) was intraperitoneally injected 1 day before the radiation treatment and then injected (10 g per mouse) every other day during the experiment. The percentage of CD8+ T cell in CD45+ immune cells (D) or tumor tissue (E) is shown. Data are shown as means ± SEM and are representative of three (A to E) independent experiments. The statistical analysis was performed by unpaired Student’s t test. *P < 0.05 and ****P < 0.0001.
图4、补充材料4
图5、补充材料5


结果五、应用IL-1可以克服肿瘤的辐射抗性
考虑到DCs中IL-1信号通路在放疗抗肿瘤活性中的重要作用,作者想测试局部给药IL-1β是否可以逆转Casp1−/−和Aim2−/−NLRP3−/−小鼠的肿瘤辐射抗性。作者将MC38细胞接种到Casp1−/−小鼠中。然后用放疗、IL-1β或放疗和IL-1β联合治疗肿瘤。结果显示移植的MC38肿瘤对放疗或IL-1β治疗均有抗性(图6A)。然而,放疗和IL-1β联合治疗克服了Casp1−/−小鼠肿瘤的辐射抗性(图6A)。同样,在Aim2−/−NLRP3−/−小鼠中,IL-1β也可使MC38肿瘤对放疗增敏(图6B)。为了验证IL-1β对WT小鼠放疗后的影响,作者对WT小鼠接种了MC38,并对肿瘤进行放疗和/或IL-1β治疗。同样,IL-1β与放疗协同控制WT小鼠的MC38肿瘤生长(图6C)。然而,IL-1r1−/−小鼠的肿瘤仍然对放疗和IL-1β单药或联合治疗具有抗性(图6D),提示IL-1β通过靶向宿主免疫细胞中的IL-1信号发挥作用。为了进一步验证IL-1信号在联合治疗DC中的作用,作者还在zDC-Cre; IL-1r1fl/fl小鼠中接种了MC38肿瘤细胞。与IL-1r1−/−小鼠的结果一致,zDC-Cre; IL-1r1fl/fl小鼠的肿瘤对放疗和IL-1β联合治疗具有抗性(图6E)。这些发现表明,给药IL-1β可以靶向DCs克服AIM2/NLRP3或Casp1缺陷小鼠的辐射抗性。



Fig. 6. The antitumor effect of IL-1 treatment after RT. Tumors were untreated or treated locally with one dose of 15-Gy (IR) radiation. Then, IL-1 (2.5 g per mice) were intratumorally injected at days 9, 11, and 13. The tumor growth curve is shown as a measure of tumor volume in Casp1−/− mice (n = 4 to 5) (A), Aim2−/−Nlrp3−/− mice (n = 6 to 8) (B), WT mice (n = 5) (C), Il1r1−/− mice (n = 5) (D), or zDCcre+- Il1r1fl/fl mice (n = 4 to 5) (E). Data are shown as mean ± SEM and are representative of three (A to E) independent experiments. The statistical analysis was performed by two-way ANOVA test. ***P < 0.001 and ****P < 0.0001.


研究结论
AIM2和NLRP3炎症小体在辐射诱导的抗肿瘤免疫中起重要作用。辐射通过AIM2和NLRP3炎症小体诱导Casp1激活,随后增加IL-1β的产生,刺激树突状细胞在受辐射肿瘤中启动CD8+ T细胞,并诱导抗肿瘤免疫作用;

原文链接
https://pubmed.ncbi.nlm.nih.gov/33963060/

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    2021-12-01 jiyangfei
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    2021-12-01 yuandd
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    2021-12-01 jjjiang0202
  5. [GetPortalCommentsPageByObjectIdResponse(id=1690692, encodeId=e1cf169069254, content=<a href='/topic/show?id=f684128e260' target=_blank style='color:#2F92EE;'>#NLRP3炎症小体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12872, encryptionId=f684128e260, topicName=NLRP3炎症小体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=720529078091, createdName=bluefate131, createdTime=Thu Nov 10 18:49:06 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349408, encodeId=13eb1349408da, content=<a href='/topic/show?id=838593e35b2' target=_blank style='color:#2F92EE;'>#辐射#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93735, encryptionId=838593e35b2, topicName=辐射)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Wed Dec 01 06:49:06 CST 2021, time=2021-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407773, encodeId=fcd3140e77317, content=<a href='/topic/show?id=a22412862b3' target=_blank style='color:#2F92EE;'>#NLR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Wed Dec 01 06:49:06 CST 2021, time=2021-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508315, encodeId=9f001508315c4, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Wed Dec 01 06:49:06 CST 2021, time=2021-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538792, encodeId=c5ed1538e9206, content=<a href='/topic/show?id=93341286ee6' target=_blank style='color:#2F92EE;'>#NLRP3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12867, encryptionId=93341286ee6, topicName=NLRP3)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=981f13051678, createdName=vera_1207, createdTime=Wed Dec 01 06:49:06 CST 2021, time=2021-12-01, status=1, ipAttribution=)]
    2021-12-01 vera_1207

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