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Hui Lu
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-44 - The Role of Microbiota on the Development of Non-Small-Cell Lung Cancer (Now Available) (ID 2055)
09:45 - 18:00 | Author(s): Hui Lu
- Abstract
Background
The functional role of microbiota on the development of cancer has attracted an accumulating attention recently. However, the impact of fecal and sputum microbiome in the formation and development of Non-small-cell lung cancer (NSCLC) are mostly unknown. Our study aimed to characterize and compare fecal and sputum microbiome of NSCLC patients with healthy control subjects, and analysis the fecal microbiome of NSCLC patients with or without brain metastasis (BM).
Method
We collected 102 fecal and 71 sputum samples from Wuhan Union Hospital. The Illumine Miseq sequencing platform was used to analyze 16S rRNA variable regions V3 and V4 in these samples. C57/BJ mice were treated with an antibiotic cocktail to postnatally deplete the microbiota. The effect of antibiotic was subsequently investigated both in xenograft model and brain metastases model.
Result
Clinical characteristics of the participants including age, gender and body mass index were matched between the compared groups. (1) The sputum microbial diversity of healthy control group (n=18) was higher than NSCLC group (n=53, P < 0.05). Genus Actinomyces was significantly more abundant in sputum samples of NSCLC patients than the healthy controls (P < 0.05), while Neisseria was more abundant in the controls. The area under the curve of genus Actinomyces used to predict lung cancer was 0.71 (95% CI: 0.69 - 0.91). (2) However, no difference in alpha diversity was showed between the fecal microbial of healthy control group (n=22) and NSCLC group (n=80). Genus Haemophilus was significantly more abundant in fecal sample of NSCLC patients than the healthy controls (P < 0.05). The area under the curve of genus Actinomyces used to predict lung cancer was 0.75 (95% CI: 0.65 - 0.84). (3) The alpha diversity of fecal microbial was similar between patients with brain metastasis group (BM+, n=18) and patients without BM group (BM-, n=32). But there were some differences in the microflora structure between the 2 groups. (4) An impaired microbiota of mouse, antibiotic treatment, promoted tumorigenesis in subcutaneous xenograft, but inhibited tumorigenesis in brain metastasis. Impaired microbiota at least partially influenced the progression of Lewis cell line through acute and chronic inflammation of the intestine.
Conclusion
The genus Actinomyces in sputum samples and Haemophilus in fecal samples were abundant in NCSLC group and exhibited moderate classification potential. The microflora structure of BM(-) and BM(+) group was significantly different. Antibiotic treatment at least partially influenced Lewis progression through acute and chronic inflammation of the intestine.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-34 - Fractalkine Attenuate Irradiation-Induced Brain Injury Through Promoting the M2 Polarization of Microglia (Now Available) (ID 2136)
10:15 - 18:15 | Author(s): Hui Lu
- Abstract
Background
Radiation-induced brain injury (RIBI) is an unavoidable adverse side-effect induced by cranial radiation therapy. The neuro-inflammation mediated by activated microglia has been proved to be a key role in RIBI by our previous researches. Studies have demonstrated that vascular endothelial cells are damaged by irradiation and Fractalkine (FKN)， a crucial mediator modulating the biological activity of microglia， is released. However, the role of FKN in RIBI was poorly understood. The aim of this study was to investigate the effect of FKN on RIBI and its underlying mechanisms.
Method
Human Umbilical Vein Endothelial Cells (HUVEC) was subjected to 10 Gy or sham irradiation, FKN expression was detected by Western blotting (WB), qRT-PCR and ELISA, γH2AX formation and nuclear translocation of p65 was analyzed by immunocytochemistry (ICC). BV-2 cells received 10-Gy irradiation after being cultured for 3 h with or without FKN (100ng/ml), or co-cultured with HUVEC. Moreover, the CX3CR1 (the receptor of FKN on microglia) wide-type (CX3CR1WT) and CX3CR1-knockdown (CX3CR1-/-) mice were employed and subjected to lateral ventricular injection (ICV) of 5 μl FKN lentivirus or vector 3 days before 10-Gy whole brain irradiation. The polarization of microglia in vitro or in hippocampus and its inflammatory factors release were evaluated through measuring the signature genes, protein and cytokines of M1/M2 phenotype by RT-PCR, WB and ELISA at different time-points after irradiation. Hippocampus neurogenesis was evaluated through detecting the proliferation marker BrdU/nestin and differentiation marker BrdU/NeuN by immunofluorescence (IF) respectively. Neurological function was evaluated by morris water maze (MWM) at 6 weeks after RIBI , and the relationship between microglia and vascular was explored by IF. Then the in vitro phagocytosis assays were performed to investigate if FKN could promote BV2’ phagocytic function.
Result
The expression of FKN in HUVEC was increased by 10 Gy irradiation, simultaneously， γH2AX formation and p65 nuclear translocation were observed. FKN regardless from exogenous or secreted by HUVEC could promote the M2 polarization of microglia and inhibit inflammatory response in vitro， it also enhanced neurogenesis in hippocampus, and improved function recovery in CX3CR1WT mice, but not in CX3CR1-/-mice after RIBI. More interestingly, activated microglia migrated to blood vessels in CX3CR1WT mice was observed in vivo by IF. What’s more, BV2 cells phagocytized more fluorescent microspheres when treated with FKN.
Conclusion
The FKN/CX3CR1 axis plays an important role in RIBI, and might be an underlying target for the treatment of radiation-induced cognitive impairment.
