Targeting the innate immune response in HNSCC
针对 HNSCC 的先天免疫反应
基本信息
- 批准号:9980195
- 负责人:
- 金额:$ 46.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAutomobile DrivingBiologicalBlood CirculationCD8-Positive T-LymphocytesCancer EtiologyCessation of lifeChemotherapy and/or radiationClinicalComplexCountryDiseaseFRAP1 geneGene Expression ProfileHead and Neck CancerHead and Neck NeoplasmsHead and Neck Squamous Cell CarcinomaHuman PapillomavirusImmuneImmune checkpoint inhibitorImmune responseImmune systemImmunologic MarkersImmunosuppressionImmunotherapeutic agentImmunotherapyIncidenceInfectionInflammatoryInnate Immune ResponseInterferon Type IIInterleukin-10Interleukin-12Malignant NeoplasmsMediatingMetastatic/RecurrentMolecularMyeloid CellsMyeloid-derived suppressor cellsNatureNivolumabPatient-Focused OutcomesPatientsPhenotypePhosphatidylinositol 4,5-DiphosphatePhosphotransferasesProteinsRoleSamplingSignal PathwaySignal TransductionSystemT cell responseT cell therapyT memory cellT-LymphocyteTestingTherapeuticTissuesTransforming Growth Factor betaTumor-associated macrophagesUnited StatesWomananimal tissueanti-PD-1anti-tumor immune responsearginasecancer therapycombatcytotoxiccytotoxic CD8 T cellsimmunogenicimprovedimproved outcomemacrophagemalignant mouth neoplasmmalignant oropharynx neoplasmmenmortalitynew therapeutic targetnovelnovel strategiesnovel therapeutic interventionnovel therapeuticsphase III trialpolarized cellpredictive signaturerecruitresponsestandard of caretargeted agenttherapeutic targettreatment strategytumortumor growthtumor microenvironmenttumor progression
项目摘要
Abstract
The immune system is a complex but highly plastic biological defense system that normally protects the host
against infection and damage. However, in some disease states, such as cancer, the usually well-orchestrated
immune response fails to protect the host and instead exacerbates disease. Because the immune system is
highly plastic, however, novel therapeutics may be able to restore normal immune responses that combat
cancer. There is a critical need to develop novel therapies for oral cancers, such as head and neck squamous
cell carcinoma (HNSCC), a deadly and disfiguring disease that accounts for an estimated 59,340 cases
(43,390 men and 15,950 women) and 12,290 deaths each year in the United States. The incidence of HNSCC
is rapidly rising in the United States and worldwide, in part due to increases in human papillomavirus (HPV)
associated oropharynx cancers. While current immune therapies hold new promise for the treatment of cancer,
the checkpoint inhibitor nivolumab (anti-PD-1) recently demonstrated only modest single agent activity in
recurrent/metastatic HNSCC, as one-year survival and response rates were only 36% and 13%, respectively,
in a Phase 3 trial. Improved therapeutic approaches that target additional mechanisms of immune escape in
combination with checkpoint inhibitors could hold promise for this disease. Our recent studies (Nature 2016)
showed that immune suppressive Tumor Associated Macrophages (TAMs) promote HNSCC immune escape.
We found that two macrophage proteins, phosphatidylinositol-4,5-bisphosphate 3-kinase gamma PI3Kγ
inhibition repolarized macrophages and synergized with anti-PD-1 to enhance recruitment and activation of
IFNγ+ cytotoxic CD8+ T cells. These results indicate that therapeutic strategies that target TAMs as well as T
cell checkpoints could improve HNSCC patient outcomes. We propose to test the overall hypothesis that
therapeutic strategies that block macrophage-mediated immune suppression will synergize with T cell targeted
therapeutics to improve outcomes in HNSCC disease. The specific aims of this proposal are: 1) To determine
how immune suppressive myeloid cells are recruited to HNSCC tumors. 2) To identify how myeloid cell
polarization is controlled during HNSCC tumor progression. 3) To identify novel immune therapeutic strategies
and immune biomarkers for HNSCC disease.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Judith A VARNER其他文献
Judith A VARNER的其他文献
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{{ truncateString('Judith A VARNER', 18)}}的其他基金
10X Chromium Connect for Single Cell Library Preparations for Translational Research
用于转化研究的单细胞文库制备的 10X Chromium Connect
- 批准号:
10430292 - 财政年份:2022
- 资助金额:
$ 46.83万 - 项目类别:
Targeting the innate immune response in HNSCC
针对 HNSCC 的先天免疫反应
- 批准号:
10586476 - 财政年份:2017
- 资助金额:
$ 46.83万 - 项目类别:
Targeting the innate immune response in HNSCC
针对 HNSCC 的先天免疫反应
- 批准号:
9763352 - 财政年份:2017
- 资助金额:
$ 46.83万 - 项目类别:
Targeting the innate immune response in HNSCC
针对 HNSCC 的先天免疫反应
- 批准号:
10216217 - 财政年份:2017
- 资助金额:
$ 46.83万 - 项目类别:
Role of PI3Kinase in Tumor Progression and Metastasis
PI3激酶在肿瘤进展和转移中的作用
- 批准号:
10375512 - 财政年份:2012
- 资助金额:
$ 46.83万 - 项目类别:
Role of PI3Kinase Gamma in Tumor Progression and Metastasis
PI3激酶γ在肿瘤进展和转移中的作用
- 批准号:
8828127 - 财政年份:2012
- 资助金额:
$ 46.83万 - 项目类别:
Role of PI3Kinase Gamma in Tumor Progression and Metastasis
PI3激酶γ在肿瘤进展和转移中的作用
- 批准号:
8844128 - 财政年份:2012
- 资助金额:
$ 46.83万 - 项目类别:
Role of PI3Kinase in Tumor Progression and Metastasis
PI3激酶在肿瘤进展和转移中的作用
- 批准号:
10116294 - 财政年份:2012
- 资助金额:
$ 46.83万 - 项目类别:
Role of PI3Kinase Gamma in Tumor Progression and Metastasis
PI3激酶γ在肿瘤进展和转移中的作用
- 批准号:
9516087 - 财政年份:2012
- 资助金额:
$ 46.83万 - 项目类别:
Role of PI3Kinase Gamma in Tumor Progression and Metastasis
PI3激酶γ在肿瘤进展和转移中的作用
- 批准号:
9033872 - 财政年份:2012
- 资助金额:
$ 46.83万 - 项目类别:
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