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         headline:Programmed cell removal by calreticulin in tissue homeostasis and cancer
         description:Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes. Macrophage-mediated programmed cell removal (PrCR) allows clearance of living cells. Here the authors show that, in mouse models, activated macrophages create an “eat me” signal via calreticulin secretion on neutrophils during peritonitis and on cancer cells, determining in both cases clearance by PrCR.
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      headline:Programmed cell removal by calreticulin in tissue homeostasis and cancer
      description:Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes. Macrophage-mediated programmed cell removal (PrCR) allows clearance of living cells. Here the authors show that, in mouse models, activated macrophages create an “eat me” signal via calreticulin secretion on neutrophils during peritonitis and on cancer cells, determining in both cases clearance by PrCR.
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            name:Stanford Cancer Institute, Stanford University
            address:
               name:Stanford Cancer Institute, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
      name:Jing Chen
      affiliation:
            name:City of Hope Comprehensive Cancer Center
            address:
               name:Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, USA
               type:PostalAddress
            type:Organization
            name:State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University
            address:
               name:State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University, Chengdu, China
               type:PostalAddress
            type:Organization
      name:Allison M. Banuelos
      affiliation:
            name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
            address:
               name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University
            address:
               name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Stanford Cancer Institute, Stanford University
            address:
               name:Stanford Cancer Institute, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
      name:Jie Liu
      affiliation:
            name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
            address:
               name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University
            address:
               name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Stanford Cancer Institute, Stanford University
            address:
               name:Stanford Cancer Institute, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
      name:Phung Gip
      affiliation:
            name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
            address:
               name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University
            address:
               name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Stanford Cancer Institute, Stanford University
            address:
               name:Stanford Cancer Institute, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
      name:Lei Cheng
      affiliation:
            name:State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University
            address:
               name:State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University, Chengdu, China
               type:PostalAddress
            type:Organization
      name:Denong Wang
      affiliation:
            name:SRI International
            address:
               name:SRI International, Menlo Park, USA
               type:PostalAddress
            type:Organization
      name:Irving L. Weissman
      url:http://orcid.org/0000-0002-9077-7467
      affiliation:
            name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
            address:
               name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University
            address:
               name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Stanford Cancer Institute, Stanford University
            address:
               name:Stanford Cancer Institute, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
            name:Stanford University
            address:
               name:Department of Pathology, Stanford University, Stanford, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, USA
      name:State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University, Chengdu, China
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University, Chengdu, China
      name:SRI International, Menlo Park, USA
      name:Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, USA
      name:Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, USA
      name:Stanford Cancer Institute, Stanford University, Stanford, USA
      name:Department of Pathology, Stanford University, Stanford, USA

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