Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn r...Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn regulates immune escape in pancreatic ductal adenocarcinoma(PDAC)^(1).On the basis of a series of studies of our laboratory,we hypothesize that a subset of pancreatic epithelial cells mimics the phenotype and function of Tregs(named quasi-Tregs or qTregs);this concept has been supported by a peer-reviewed commentary^(2).Moreover,evidence suggests that tumor epithelial cells can mimic other types of immune cells and participate in the formation of a tumor immunosuppressive microenvironment(TIM).展开更多
Pancreatic ductal adenocarcinoma(PDAC)is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment.PDAC overcomes these restrictions by employing unconventional tactics for th...Pancreatic ductal adenocarcinoma(PDAC)is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment.PDAC overcomes these restrictions by employing unconventional tactics for the procurement and usage of fuel sources.The substantial reprogramming of PDAC cell metabolism is driven by oncogene-mediated cell-autonomous pathways.PDAC cells use glucose,glutamine,and lipids for energy and depend on autophagy and macropinocytosis for survival and growth.They also interact metabolically with non-cancerous cells,aiding tumor progression.Many clinical trials focusing on altered metabolism are ongoing.Understanding the metabolic regulation of PDAC cells will not only help to increase understanding of the mechanisms of disease progression but also provide insights for the development of new diagnostic and therapeutic approaches.展开更多
In recent study published on Nature Medicine,Bockorny et al.1 performed a single-arm phase IIa trial(COMBAT study,NCT02826486)to evaluate safety,efficacy,immunobiological changes,and potential biomarkers for the CXCR4...In recent study published on Nature Medicine,Bockorny et al.1 performed a single-arm phase IIa trial(COMBAT study,NCT02826486)to evaluate safety,efficacy,immunobiological changes,and potential biomarkers for the CXCR4 inhibitor BL-8040,combined with a PD-1 antagonist(pembrolizumab)as a second-line or third-line treatment for patients with metastatic PDAC.This evidence translates the theory of reprogramming tumor immunosuppressive microenvironment into clinical practice and supports that targeting chemokines/chemokine receptors facilitates the immunotherapy of pancreatic ductal adenocarcinoma(Fig.1).展开更多
基金This work was funded by the National Natural Science Foundation of China(Grant No.81772633)the Taishan Researchers Program of Shandong Province,and the Major State Basic Research Development Program of Natural Science Foundation of Shandong Province in China(Grant No.ZR2020ZD11).
文摘Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn regulates immune escape in pancreatic ductal adenocarcinoma(PDAC)^(1).On the basis of a series of studies of our laboratory,we hypothesize that a subset of pancreatic epithelial cells mimics the phenotype and function of Tregs(named quasi-Tregs or qTregs);this concept has been supported by a peer-reviewed commentary^(2).Moreover,evidence suggests that tumor epithelial cells can mimic other types of immune cells and participate in the formation of a tumor immunosuppressive microenvironment(TIM).
基金financially supported by the National Science Fund for National Natural Science Foundation of China(No.82125026,82330081)Taishan Scholars Program of Shandong Province(No.Ts20190987)Major State Basic Research Development Program of Natural Science Foundation of Shandong Province in China(No.ZR2020ZD11).
文摘Pancreatic ductal adenocarcinoma(PDAC)is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment.PDAC overcomes these restrictions by employing unconventional tactics for the procurement and usage of fuel sources.The substantial reprogramming of PDAC cell metabolism is driven by oncogene-mediated cell-autonomous pathways.PDAC cells use glucose,glutamine,and lipids for energy and depend on autophagy and macropinocytosis for survival and growth.They also interact metabolically with non-cancerous cells,aiding tumor progression.Many clinical trials focusing on altered metabolism are ongoing.Understanding the metabolic regulation of PDAC cells will not only help to increase understanding of the mechanisms of disease progression but also provide insights for the development of new diagnostic and therapeutic approaches.
基金funded by The National Natural Science Foundation of China(81772633)the Taishan Scholars Program of Shandong Province.
文摘In recent study published on Nature Medicine,Bockorny et al.1 performed a single-arm phase IIa trial(COMBAT study,NCT02826486)to evaluate safety,efficacy,immunobiological changes,and potential biomarkers for the CXCR4 inhibitor BL-8040,combined with a PD-1 antagonist(pembrolizumab)as a second-line or third-line treatment for patients with metastatic PDAC.This evidence translates the theory of reprogramming tumor immunosuppressive microenvironment into clinical practice and supports that targeting chemokines/chemokine receptors facilitates the immunotherapy of pancreatic ductal adenocarcinoma(Fig.1).
