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Pei Wang,1,2,* Ming-Hao Xu,3,* Wen-Xin Xu,3,* Zi-Ying Dong,4 Ying-Hao Shen,3 Wen-Zheng Qin1 1Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Digestive Medicine, Wuwei People’s Hospital, Wuwei City, Gansu Province, 733000, People’s Republic of China; 3Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of CT/MRI Center, Wuwei People’s Hospital, Wuwei City, Gansu Province, 733000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen-Zheng Qin, Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64041990, Email qin.wenzheng@zs-hospital.sh.cn Ying-Hao Shen, Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64041990, Email syh12268@163.comBackground: Anti-programmed death-1 (PD1) antibodies have changed the treatment landscape for hepatocellular carcinoma (HCC) and exhibit promising treatment efficacy. However, the majority of HCCs still do not respond to anti-PD-1 therapy.Methods: We analyzed the expression of CXCL9 in blood samples from patients who received anti-PD-1 therapy and evaluated its correlation with clinicopathological characteristics and treatment outcomes. Based on the results of Cox regression analysis, a nomogram was established for predicting HCC response to anti-PD-1 therapy. qRT‒PCR and multiple immunofluorescence assays were utilized to analyze the proportions of N1-type neutrophils in vitro and in tumor samples, respectively.Results: The nomogram showed good predictive efficacy in the training and validation cohorts and may be useful for guiding clinical treatment of HCC patients. We also found that HCC cell-derived CXCL9 promoted N1 polarization of neutrophils in vitro and that AMG487, a specific CXCR3 inhibitor, significantly blocked this process. Moreover, multiple immunofluorescence (mIF) showed that patients with higher serum CXCL9 levels had greater infiltration of the N1 phenotype of tumor-associated neutrophils (TANs).Conclusion: Our study highlights the critical role of CXCL9 as an effective biomarker of immunotherapy efficacy and in promoting the polarization of N1-type neutrophils; thus, targeting the CXCL9-CXCR3 axis could represent a novel pharmaceutical strategy to enhance immunotherapy for HCC.Keywords: CXCL9, anti-PD-1 antibody, N1 polarization of neutrophils, nomogram

Lei Wei,1,* Dong Xu,2,* Yechang Qian,1 Guoyi Huang,1 Wei Ma,1 Fangying Liu,1 Yanhua Shen,1 Zhongfu Wang,1 Li Li,1 Shanfang Zhang,1 Yafang Chen1 1Department of Respiratory Disease, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 2Medical College of Soochow University, Suzhou, People's Republic of China *These authors contributed equally to this work Objective: To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD) patients and explore the possible therapeutic targets. Methods: The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus. After data preprocessing with the Affy package, Student’s t-test was employed to identify the differentially expressed genes (DEGs). The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA. Furthermore, we constructed a protein–protein interaction (PPI) network for DEGs. The surfactant protein D (SP-D) serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction, respectively. Results: A total of 39 up- and 15 downregulated DEGs were screened. Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process. Moreover, we also found that HLA-A has the highest degree in the PPI network. The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P