首页|Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic ductal adenocarcinoma:a phaseⅠb/Ⅱ trial

Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic ductal adenocarcinoma:a phaseⅠb/Ⅱ trial

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Advanced pancreatic ductal adenocarcinoma(PDAC)has a dismal prognosis.Immunotherapy alone offers limited efficacy,but it is still unknown whether its combination with chemotherapy could offer synergistic anti-tumor effects.This phase Ⅰb/Ⅱ study evaluated the safety and efficacy of combining toripalimab with the gemcitabine plus nab-paclitaxel(GnP)regimen as first-line treatment for locally advanced or metastatic PDAC and explored predictive biomarkers(ChiCTR2000032293).The primary endpoints were safety and overall survival(OS).The secondary outcomes were objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Immune-related biomarkers including programmed death-ligand 1(PD-L1)expression,genetic status,cytokine levels,and spatial features of the tumor immune microenviroment(TIME)were investigated.Neither serious treatment-related adverse events nor grade 4 immune-related adverse events were reported.Among the 72 patients,the median OS was 8.9 months,12-month OS rate was 31.9％,with median PFS of 5.6 months,ORR of 33.3％,and DCR of 90.3％.Higher PD-L1 expression,without liver metastases were associated with higher ORR,however these factors could not effectively distinguish responders and non-responders.Importantly,dendritic cells-T helper cells-cytotoxic T lymphocytes(DC-Th-CTL)enriched immune niche and their spatial interactions were dominant predictors of response based on TIME analysis using a cyclic multiplex tissue staining assay,with an area under the curve value of 0.8.Overall,GnP plus toripalimab exhibited good safety and differentiated efficacy in selected population,and the spatial interactions of DC-Th-CTL represent promising predictors to efficacy of immunochemotherapy in locally advanced or metastatic PDAC.

Ke Cheng、Xiaoying Li、Wanrui Lv、Gang Zhao、Ruihan Zhou、Chen Chang、Heqi Yang、Ruizhen Li、Zhiping Li、Ye Chen、Cheng Yi、Ouying Yan、Chaoxin Xiao、Yi Zhang、Junjie Xiong、Zixin Huang、Weikang Shao、Xin You、Wenhao Guo、Du He、Wenwu Ling、Rui Wang、Bole Tian、Chengjian Zhao、Dan Cao

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Division of Abdominal Tumor,Department of Medical Oncology,Cancer Center and State Key Laboratory of Biological Therapy,West China Hospital,Sichuan University,Chengdu,Sichuan,China

Department of Oncology,Meishan City People's Hospital,Meishan,Sichuan,China

State Key Laboratory of Biotherapy and Cancer Center,Sichuan University and Collaborative Innovation Center,West China Hospital,Chengdu,Sichuan,China

Pancreatic Division,Department of General Surgery,West China Hospital,Sichuan University,Chengdu,Sichuan,China

Department of General Surgery,ChengDu ShangJing NanFu Hospital,Chengdu,Sichuan,China

Department of Radiology,West China Hospital,Sichuan University,Chengdu,Sichuan,China

Department of Radiology,West China Tianfu Hospital,Sichuan University,Chengdu,Sichuan,China

Genecast Biotechnology Co.Ltd,Wuxi,China

Department of Pathology,West China Hospital,Sichuan University,Chengdu,Sichuan,China

Department of Medical Ultrasound,West China Hospital of Sichuan University,Chengdu,Sichuan,China

Department of Gastroenterology,West China Hospital,Sichuan University,Chengdu,Sichuan,China

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2024

10.1038/s41392-024-02031-8

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

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年,卷(期)：2024.9(12)