High dose radiation therapy to direct immune responses to pancreatic cancer
高剂量放射治疗引导胰腺癌的免疫反应
基本信息
- 批准号:10676741
- 负责人:
- 金额:$ 38.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-06-15 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAntigen PresentationBioinformaticsCellsCellular immunotherapyClinicalClinical ResearchCombination immunotherapyCombined Modality TherapyCross PresentationDataDendritic CellsDevelopmentDiseaseDistantDoseEnvironmentFailureFractionationGenetic EngineeringGoalsGrowth and Development functionHead and Neck Squamous Cell CarcinomaImmuneImmune responseImmunityImmunocompetentImmunologyImmunotherapyInfiltrationKnowledgeMalignant NeoplasmsMalignant neoplasm of pancreasMediatingModelingMusNeoplasm MetastasisOrgan PreservationOutcomePatient-Focused OutcomesPatientsPhenotypePlayPopulationPre-Clinical ModelPredispositionRadiationRadiation Dose UnitRadiation InteractionRadiation therapyRegulationResearch DesignResectableResidual stateRoleSamplingSiteT cell responseT-LymphocyteTestingTimeTumor AntigensTumor ImmunityVaccinesanti-tumor immune responseantigen-specific T cellscancer cellcheckpoint therapydraining lymph nodefunctional restorationgenetic analysisimmune cell infiltrateimmunogenicimplantationimprovedimproved outcomein situ vaccinenovelpre-clinicalpreventradiation effectradiation responseresponsesuccesstherapy outcometumortumor growth
项目摘要
PROJECT SUMMARY
The critical preliminary data for this proposal is that in preclinical models, pre-existing tumor-resident T cells
are both necessary and sufficient for tumor control by radiation therapy and immunotherapy. We demonstrate
that in poorly immunogenic tumors, cross-presenting dendritic cells in the tumor-draining lymph node may be
playing no significant role in tumor control. In these models, radiation and immunotherapy are an effective
means of local control but fail to engender new systemic immunity. The aim of this proposal is to understand
how radiation interacts with tumor resident T cells for local control, and how to restore cross-presentation of
tumor-associated antigens to generate new systemic anti-tumor immune responses. We hypothesize that the
endogenous vaccine effect of radiation therapy is limited in poorly immunogenic tumors, and current success
relies on amplifying pre-existing anti-tumor immunity. The specific aims of this study are to 1: Test the
hypothesis that in the presence of pre-existing immunity, tumor control by radiation therapy and
immunotherapy occurs independent of cross-presentation and new immune responses; 2: Test the hypothesis
that deficient DC cross-presentation limits the ability of radiation therapy to initiate new systemic anti-tumor
immune responses; 3: Test the hypothesis that regulation of antigen presentation and cross-presenting DC
can be assessed in patient tumors using genetic analysis. Our study design incorporates CT-guided radiation
therapy and results are validated in multiple tumor models including those from genetically engineered
spontaneous models, using a range of RT doses and fractionations. Our analyses of clinical samples use high
quality bioinformatic approaches that allow us to evaluate the infiltrating immune cells and antigen presentation
in patient tumors. These are applied to a unique clinical study that allows us to validate our preclinical
observations in patients.
项目总结
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
CNS side effects of immune checkpoint inhibitors: preclinical models, genetics and multimodality therapy.
- DOI:10.2217/imt-2017-0056
- 发表时间:2017-09
- 期刊:
- 影响因子:2.8
- 作者:McGinnis GJ;Raber J
- 通讯作者:Raber J
Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy.
- DOI:10.18632/oncotarget.11823
- 发表时间:2016-11-29
- 期刊:
- 影响因子:0
- 作者:Crittenden MR;Baird J;Friedman D;Savage T;Uhde L;Alice A;Cottam B;Young K;Newell P;Nguyen C;Bambina S;Kramer G;Akporiaye E;Malecka A;Jackson A;Gough MJ
- 通讯作者:Gough MJ
Amplifying IFN-γ Signaling in Dendritic Cells by CD11c-Specific Loss of SOCS1 Increases Innate Immunity to Infection while Decreasing Adaptive Immunity.
- DOI:10.4049/jimmunol.1700909
- 发表时间:2018-01-01
- 期刊:
- 影响因子:0
- 作者:Alice AF;Kramer G;Bambina S;Baird JR;Bahjat KS;Gough MJ;Crittenden MR
- 通讯作者:Crittenden MR
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy.
- DOI:10.1371/journal.pone.0157164
- 发表时间:2016
- 期刊:
- 影响因子:3.7
- 作者:Young KH;Baird JR;Savage T;Cottam B;Friedman D;Bambina S;Messenheimer DJ;Fox B;Newell P;Bahjat KS;Gough MJ;Crittenden MR
- 通讯作者:Crittenden MR
A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma.
- DOI:10.1186/s40425-016-0149-6
- 发表时间:2016
- 期刊:
- 影响因子:10.9
- 作者:Crocenzi T;Cottam B;Newell P;Wolf RF;Hansen PD;Hammill C;Solhjem MC;To YY;Greathouse A;Tormoen G;Jutric Z;Young K;Bahjat KS;Gough MJ;Crittenden MR
- 通讯作者:Crittenden MR
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Michael James Gough其他文献
Michael James Gough的其他文献
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{{ truncateString('Michael James Gough', 18)}}的其他基金
DNASE1L3 regulation of anti-tumor immune responses following radiation therapy
DNASE1L3 对放射治疗后抗肿瘤免疫反应的调节
- 批准号:
10577698 - 财政年份:2023
- 资助金额:
$ 38.4万 - 项目类别:
Rewiring the myeloid cell response to adjuvants to improve tumor control
重新连接骨髓细胞对佐剂的反应以改善肿瘤控制
- 批准号:
10064141 - 财政年份:2019
- 资助金额:
$ 38.4万 - 项目类别:
Rewiring the myeloid cell response to adjuvants to improve tumor control
重新连接骨髓细胞对佐剂的反应以改善肿瘤控制
- 批准号:
10534119 - 财政年份:2019
- 资助金额:
$ 38.4万 - 项目类别:
Rewiring the myeloid cell response to adjuvants to improve tumor control
重新连接骨髓细胞对佐剂的反应以改善肿瘤控制
- 批准号:
10305679 - 财政年份:2019
- 资助金额:
$ 38.4万 - 项目类别:
High dose radiation therapy to direct immune responses to pancreatic cancer
高剂量放射治疗引导胰腺癌的免疫反应
- 批准号:
10411997 - 财政年份:2014
- 资助金额:
$ 38.4万 - 项目类别:
High dose radiation therapy to direct immune responses to pancreatic cancer
高剂量放射治疗引导胰腺癌的免疫反应
- 批准号:
10160635 - 财政年份:2014
- 资助金额:
$ 38.4万 - 项目类别:
High dose radiation therapy to direct immune responses to pancreatic cancer
高剂量放射治疗引导胰腺癌的免疫反应
- 批准号:
8760163 - 财政年份:2014
- 资助金额:
$ 38.4万 - 项目类别:
High dose radiation therapy to direct immune responses to pancreatic cancer
高剂量放射治疗引导胰腺癌的免疫反应
- 批准号:
9815641 - 财政年份:2014
- 资助金额:
$ 38.4万 - 项目类别:
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