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CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans.

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Title: CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans.
Authors: Beatty, Gregory L., Chiorean, Elena G., Fishman, Matthew P., Saboury, Babak, Teitelbaum, Ursina R., Weijing Sun, Huhn, Richard D., Wenru Song, Dongguang Li, Sharp, Leslie L., Torigian, Drew A., O'Dwyer, Peter J., Vonderheide, Robert H.
Source: Science (pre-March 2025). 3/25/2011, Vol. 331 Issue 6024, p1612-1616. 5p.
Subjects: Immunosuppression, Tumor necrosis factors, Pancreatic cancer, Cancer patients, Cohort analysis, Adenocarcinoma, Ductal carcinoma, Antineoplastic agents
Abstract: Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans.
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  Data: <searchLink fieldCode="AR" term="%22Beatty%2C+Gregory+L%2E%22">Beatty, Gregory L.</searchLink><br /><searchLink fieldCode="AR" term="%22Chiorean%2C+Elena+G%2E%22">Chiorean, Elena G.</searchLink><br /><searchLink fieldCode="AR" term="%22Fishman%2C+Matthew+P%2E%22">Fishman, Matthew P.</searchLink><br /><searchLink fieldCode="AR" term="%22Saboury%2C+Babak%22">Saboury, Babak</searchLink><br /><searchLink fieldCode="AR" term="%22Teitelbaum%2C+Ursina+R%2E%22">Teitelbaum, Ursina R.</searchLink><br /><searchLink fieldCode="AR" term="%22Weijing+Sun%22">Weijing Sun</searchLink><br /><searchLink fieldCode="AR" term="%22Huhn%2C+Richard+D%2E%22">Huhn, Richard D.</searchLink><br /><searchLink fieldCode="AR" term="%22Wenru+Song%22">Wenru Song</searchLink><br /><searchLink fieldCode="AR" term="%22Dongguang+Li%22">Dongguang Li</searchLink><br /><searchLink fieldCode="AR" term="%22Sharp%2C+Leslie+L%2E%22">Sharp, Leslie L.</searchLink><br /><searchLink fieldCode="AR" term="%22Torigian%2C+Drew+A%2E%22">Torigian, Drew A.</searchLink><br /><searchLink fieldCode="AR" term="%22O'Dwyer%2C+Peter+J%2E%22">O'Dwyer, Peter J.</searchLink><br /><searchLink fieldCode="AR" term="%22Vonderheide%2C+Robert+H%2E%22">Vonderheide, Robert H.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 3/25/2011, Vol. 331 Issue 6024, p1612-1616. 5p.
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  Data: <searchLink fieldCode="DE" term="%22Immunosuppression%22">Immunosuppression</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+necrosis+factors%22">Tumor necrosis factors</searchLink><br /><searchLink fieldCode="DE" term="%22Pancreatic+cancer%22">Pancreatic cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+patients%22">Cancer patients</searchLink><br /><searchLink fieldCode="DE" term="%22Cohort+analysis%22">Cohort analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Adenocarcinoma%22">Adenocarcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Ductal+carcinoma%22">Ductal carcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Antineoplastic+agents%22">Antineoplastic agents</searchLink>
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  Data: Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1126/science.1198443
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        Text: English
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    Subjects:
      – SubjectFull: Immunosuppression
        Type: general
      – SubjectFull: Tumor necrosis factors
        Type: general
      – SubjectFull: Pancreatic cancer
        Type: general
      – SubjectFull: Cancer patients
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      – SubjectFull: Cohort analysis
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      – SubjectFull: Adenocarcinoma
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              Text: 3/25/2011
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