FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2003298559> ?p ?o ?g. }

• W2003298559 abstract "A hallmark of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDA) is a profound immune infiltrate dominated by myeloid cells with a scarcity of T cells. Immune suppression imposed by this early immune reaction to PDA represents a significant clinical challenge to T cell immunotherapy. To circumvent this immune suppression, we have studied CD40 agonists for their well-recognized ability to induce potent T cell dependent anti-tumor immunity. However, in our studies using the KPC mouse model of PDA (KrasG12D/+ Trp53R172H/+ Pdx-1 Cre), we have found that delivery of a CD40 agonist alone or in combination with chemotherapy is unable to induce productive T cell immunosurveillance. Here, we examine barriers to the development of anti-tumor T cell immunity in PDA. By transplanting PDA tumor cells or whole PDA tumor tissue obtained from tumor-bearing KPC mice into syngeneic littermates, we demonstrate that a CD40 agonist (FGK45) in combination with gemcitabine chemotherapy can synergize to induce productive anti-tumor immunity leading to complete and sustained regression of established subcutaneous tumors (IgG2a alone – 0%; gemcitabine alone – 0%; FGK45 alone – 38%; gemcitabine + FGK45 – 71%; p < 0.001). In contrast to our findings in the KPC model, depletion of either CD4 (GK1.5) or CD8 (2.43) T cells abolished this effect (IgG2a alone – 0%; gemcitabine + FGK45 – 75%; gemcitabine + FGK45 + GK1.5 – 0%; gemcitabine + FGK45 + 2.43 – 14%; p <0.001). This observation suggested that PDA cells retain their immunogenicity and are capable of being recognized and targeted by T cells. To examine the ability of combination therapy (gemcitabine + FGK45) to induce T cell dependent anti-tumor immunity against spontaneously arising PDA, KPC mice treated with combination therapy were challenged subcutaneously two weeks later with PDA cells. However, no immune protection to tumor challenge was observed suggesting a failure to induce tumor-specific T cell immunity. To determine whether systemic immune suppression within KPC mice may inhibit the ability to induce productive T cell immunity, we next transplanted PDA tumor cells subcutaneously into KPC mice with ultrasound-confirmed PDA tumors. We found that combination therapy (gemcitabine + FGK45) delivered to these KPC mice bearing two tumors (i.e. implanted tumor plus a spontaneously arising PDA tumor) could elicit an anti-tumor T cell immune response capable of inducing tumor regression of the subcutaneously implanted tumor (Control – 0%; gemcitabine + FGK45 – 100%; p <0.001). Moreover, by delivering combination therapy to KPC animals in this “two tumor” system, we observed by immunohistochemistry an unprecedented and robust T cell infiltrate, comprised of both CD4 and CD8 T cells, into the spontaneously arising PDA tumor. Our findings suggest that ineffective T cell priming rather than immunoediting may limit T cell immunosurveillance in PDA – a finding that has important implications into the design of cancer immunotherapy for this disease.This abstract is also presented as Poster B84. Citation Format: Gregory L. Beatty, Rafi Winograd, Rebecca Evans, Santiago Lombo Luque, Patrick Guirnalda, Robert H. Vonderheide. Restoring T cell immuno-surveillance in pancreatic carcinoma using CD40 agonists. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr PR4." @default.
• W2003298559 created "2016-06-24" @default.
• W2003298559 creator A5007519779 @default.
• W2003298559 creator A5013138569 @default.
• W2003298559 creator A5014753848 @default.
• W2003298559 creator A5040750947 @default.
• W2003298559 creator A5051182961 @default.
• W2003298559 creator A5060310630 @default.
• W2003298559 date "2013-01-01" @default.
• W2003298559 modified "2023-09-25" @default.
• W2003298559 title "Abstract PR4: Restoring T cell immuno-surveillance in pancreatic carcinoma using CD40 agonists." @default.
• W2003298559 doi "https://doi.org/10.1158/1538-7445.tumimm2012-pr4" @default.
• W2003298559 hasPublicationYear "2013" @default.
• W2003298559 type Work @default.
• W2003298559 sameAs 2003298559 @default.
• W2003298559 citedByCount "0" @default.
• W2003298559 crossrefType "proceedings-article" @default.
• W2003298559 hasAuthorship W2003298559A5007519779 @default.
• W2003298559 hasAuthorship W2003298559A5013138569 @default.
• W2003298559 hasAuthorship W2003298559A5014753848 @default.
• W2003298559 hasAuthorship W2003298559A5040750947 @default.
• W2003298559 hasAuthorship W2003298559A5051182961 @default.
• W2003298559 hasAuthorship W2003298559A5060310630 @default.
• W2003298559 hasConcept C121608353 @default.
• W2003298559 hasConcept C126322002 @default.
• W2003298559 hasConcept C154317977 @default.
• W2003298559 hasConcept C167672396 @default.
• W2003298559 hasConcept C202751555 @default.
• W2003298559 hasConcept C203014093 @default.
• W2003298559 hasConcept C2776090121 @default.
• W2003298559 hasConcept C2776885095 @default.
• W2003298559 hasConcept C2777701055 @default.
• W2003298559 hasConcept C2780210213 @default.
• W2003298559 hasConcept C2780258809 @default.
• W2003298559 hasConcept C39347974 @default.
• W2003298559 hasConcept C502942594 @default.
• W2003298559 hasConcept C55493867 @default.
• W2003298559 hasConcept C71924100 @default.
• W2003298559 hasConcept C86803240 @default.
• W2003298559 hasConcept C8891405 @default.
• W2003298559 hasConceptScore W2003298559C121608353 @default.
• W2003298559 hasConceptScore W2003298559C126322002 @default.
• W2003298559 hasConceptScore W2003298559C154317977 @default.
• W2003298559 hasConceptScore W2003298559C167672396 @default.
• W2003298559 hasConceptScore W2003298559C202751555 @default.
• W2003298559 hasConceptScore W2003298559C203014093 @default.
• W2003298559 hasConceptScore W2003298559C2776090121 @default.
• W2003298559 hasConceptScore W2003298559C2776885095 @default.
• W2003298559 hasConceptScore W2003298559C2777701055 @default.
• W2003298559 hasConceptScore W2003298559C2780210213 @default.
• W2003298559 hasConceptScore W2003298559C2780258809 @default.
• W2003298559 hasConceptScore W2003298559C39347974 @default.
• W2003298559 hasConceptScore W2003298559C502942594 @default.
• W2003298559 hasConceptScore W2003298559C55493867 @default.
• W2003298559 hasConceptScore W2003298559C71924100 @default.
• W2003298559 hasConceptScore W2003298559C86803240 @default.
• W2003298559 hasConceptScore W2003298559C8891405 @default.
• W2003298559 hasLocation W20032985591 @default.
• W2003298559 hasOpenAccess W2003298559 @default.
• W2003298559 hasPrimaryLocation W20032985591 @default.
• W2003298559 hasRelatedWork W1506647723 @default.
• W2003298559 hasRelatedWork W2014896047 @default.
• W2003298559 hasRelatedWork W2019420147 @default.
• W2003298559 hasRelatedWork W2252527952 @default.
• W2003298559 hasRelatedWork W2321970604 @default.
• W2003298559 hasRelatedWork W2333535228 @default.
• W2003298559 hasRelatedWork W2395000660 @default.
• W2003298559 hasRelatedWork W2406989857 @default.
• W2003298559 hasRelatedWork W2496937664 @default.
• W2003298559 hasRelatedWork W2537973974 @default.
• W2003298559 hasRelatedWork W2563595159 @default.
• W2003298559 hasRelatedWork W2740769512 @default.
• W2003298559 hasRelatedWork W2752653332 @default.
• W2003298559 hasRelatedWork W2773086365 @default.
• W2003298559 hasRelatedWork W2795515854 @default.
• W2003298559 hasRelatedWork W2887004316 @default.
• W2003298559 hasRelatedWork W2896143580 @default.
• W2003298559 hasRelatedWork W2956922957 @default.
• W2003298559 hasRelatedWork W3049151577 @default.
• W2003298559 hasRelatedWork W3180806010 @default.
• W2003298559 isParatext "false" @default.
• W2003298559 isRetracted "false" @default.
• W2003298559 magId "2003298559" @default.
• W2003298559 workType "article" @default.