Epithelium-derived alarmins role in breast cancer immunoprevention
上皮源性警报素在乳腺癌免疫预防中的作用
基本信息
- 批准号:10000863
- 负责人:
- 金额:$ 77.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAllergic inflammationAnimal ModelAntigen PresentationAutomobile DrivingBRCA1 geneBiological AssayBlocking AntibodiesBreastBreast Cancer ModelBreast Cancer PreventionBreast CarcinogenesisBreast Epithelial CellsCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCancer EtiologyCellsCessation of lifeClinicClinicalClinical TrialsDNA DamageDNA Sequence AlterationDevelopmentDiseaseDisseminated Malignant NeoplasmDouble-Blind MethodEpithelialEpithelial CellsEpitheliumFoundationsGlandGoalsImmuneImmune responseImmune systemImmunityImmunologic FactorsImmunotherapeutic agentImmunotherapyIn SituIn VitroIndividualInflammationInterleukinsLeadLesionMalignant - descriptorMalignant NeoplasmsMammary glandMediatingMemoryMolecularNatureOutcomePathway interactionsPatientsPatternPhasePremalignant CellRandomizedRecurrenceRegulatory T-LymphocyteResearchResolutionRoleShapesSignal TransductionSkinSkin CancerStressSurveysT cell responseT-Cell ActivationT-LymphocyteTSLP geneTestingTherapeuticTherapeutic UsesTissuesTransgenic AnimalsTumor ImmunityTumor SuppressionUnited StatesWomanadaptive immune responseadaptive immunityadenomaadvanced diseasebreast lesioncancer invasivenesscancer preventioncombatcytokinecytotoxiceffector T cellepidemiology studyhigh riskhigh risk populationimmune activationknockout animalmalignant breast neoplasmmammary epitheliummutation carrierneoplasticnew therapeutic targetnovelpremalignantpreventrelease factorresponseskin cancer preventiontumortumor immunology
项目摘要
Project Summary/Abstract:
Advances in cancer immunology has led to the successful use of patients' own immune cells to combat
metastatic cancers. However, the therapeutic potential of the immune system in eliminating premalignant cells
and preventing their progression to invasive cancers is unclear. To determine the benefit of activating the
immune system to prevent cancer development and recurrence, we study the immune pathways that lead to
effective immune activation against early phases of breast cancer development. Breast cancer is the most
common internal cancer and second cause of cancer deaths among women in the United States. Importantly,
the individuals at high risk of developing breast cancer due to underlying genetic mutations and those with
premalignant lesions can be clinically identified and treated. Therefore, discovering an effective approach to
activate the patients' own immune system against early breast precursor lesions may yield a lasting memory
that can prevent breast cancer development and recurrence in this high-risk population. Our previous studies
have demonstrated that a skin-derived immune factor called thymic stromal lymphopoietin (TSLP) suppresses
the early stages of skin and breast cancer development. We have been able to extend these finding to clinics
through a randomized double-blind clinical trial in which we find TSLP induction to promote a robust immune
activation against skin cancer precursors and their complete clearance. In order to determine the precise
mechanism of TSLP-induced immune response against early premalignant cells in the breast, and to extend
our findings to other similar immune factors in high-risk patients, we aim to (1) determine the immune cells and
signals that target breast premalignant cells in response to TSLP, (2) investigate the role of other immune
factors released by breast cells that can induce immune response to block breast cancer development, and (3)
determine the factors that are driving the immune response in the breast glands of patients with genetic
mutations and utilize them for induction of an optimal immune response against early breast cancer. The
outcomes of the proposed research will establish a foundation for the use of the immune system in blocking
breast cancer development and provide novel therapeutic targets for breast cancer immunoprevention.
项目概要/摘要:
癌症免疫学的进步已经成功地利用患者自身的免疫细胞来对抗
转移性癌症然而,免疫系统在消除癌前细胞方面的治疗潜力
以及如何阻止其发展为侵袭性癌症尚不清楚。要确定激活
免疫系统,以防止癌症的发展和复发,我们研究免疫途径,导致
有效的免疫激活对乳腺癌发展的早期阶段。乳腺癌是世界上
常见的内部癌症和癌症死亡的第二个原因在美国妇女。重要的是,
由于潜在的基因突变而具有患乳腺癌高风险的个体和那些
可以在临床上识别和治疗癌前病变。因此,找到一种有效的方法,
激活患者自身的免疫系统对抗早期乳腺癌前病变可能会产生持久的记忆
可以预防乳腺癌在这个高危人群中的发展和复发。我们以前的研究
已经证明,一种称为胸腺基质淋巴细胞生成素(TSLP)的皮肤源性免疫因子抑制了
皮肤癌和乳腺癌发展的早期阶段。我们已经能够将这些发现扩展到诊所
通过一项随机双盲临床试验,我们发现TSLP诱导可以促进强大的免疫,
激活皮肤癌前体并完全清除。为了确定
TSLP诱导的针对乳腺早期癌前细胞的免疫应答的机制,
我们的研究结果与高危患者中的其他类似免疫因素相似,我们的目标是(1)确定免疫细胞,
靶向乳腺癌前病变细胞的信号,(2)研究其他免疫系统的作用。
由乳腺细胞释放的因子,其可以诱导免疫应答以阻断乳腺癌的发展,以及(3)
确定驱动遗传性乳腺癌患者乳腺免疫反应的因素,
突变,并利用它们来诱导针对早期乳腺癌的最佳免疫应答。的
拟议研究的结果将为免疫系统在阻断
为乳腺癌的免疫预防提供了新的治疗靶点。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Shadmehr Demehri其他文献
Shadmehr Demehri的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Shadmehr Demehri', 18)}}的其他基金
Immunity to commensal papillomaviruses for cancer therapy
对共生乳头瘤病毒的免疫用于癌症治疗
- 批准号:
10397664 - 财政年份:2021
- 资助金额:
$ 77.29万 - 项目类别:
Immunity to commensal papillomaviruses for cancer therapy
对共生乳头瘤病毒的免疫用于癌症治疗
- 批准号:
10209691 - 财政年份:2021
- 资助金额:
$ 77.29万 - 项目类别:
Immunity to commensal papillomaviruses for cancer therapy
对共生乳头瘤病毒的免疫用于癌症治疗
- 批准号:
10625967 - 财政年份:2021
- 资助金额:
$ 77.29万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10633109 - 财政年份:2019
- 资助金额:
$ 77.29万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
9973215 - 财政年份:2019
- 资助金额:
$ 77.29万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10617947 - 财政年份:2019
- 资助金额:
$ 77.29万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10228570 - 财政年份:2019
- 资助金额:
$ 77.29万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10844016 - 财政年份:2019
- 资助金额:
$ 77.29万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10413211 - 财政年份:2019
- 资助金额:
$ 77.29万 - 项目类别:
Epithelium-derived alarmins role in breast cancer immunoprevention
上皮源性警报素在乳腺癌免疫预防中的作用
- 批准号:
10468153 - 财政年份:2018
- 资助金额:
$ 77.29万 - 项目类别:
相似海外基金
3-Dimensional genomic architecture in innate lymphoid cells and allergic inflammation
先天淋巴细胞和过敏性炎症的三维基因组结构
- 批准号:
10417585 - 财政年份:2022
- 资助金额:
$ 77.29万 - 项目类别:
The Effect of Allergic Inflammation on Ovarian Reserve Loss Associated with Endometrioma
过敏性炎症对子宫内膜异位症相关卵巢储备功能丧失的影响
- 批准号:
22K16884 - 财政年份:2022
- 资助金额:
$ 77.29万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The regulatory roles of basophils in skin allergic inflammation by using single-cell RNA-seq analysis
利用单细胞 RNA-seq 分析嗜碱性粒细胞在皮肤过敏性炎症中的调节作用
- 批准号:
22K07115 - 财政年份:2022
- 资助金额:
$ 77.29万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
3-Dimensional genomic architecture in innate lymphoid cells and allergic inflammation
先天淋巴细胞和过敏性炎症的三维基因组结构
- 批准号:
10650334 - 财政年份:2022
- 资助金额:
$ 77.29万 - 项目类别:
Regulators of Rho GTPases in allergic inflammation: Characterizing the role of RhoGDIs in the release of pro-inflammatory mediators from mast cells
过敏性炎症中 Rho GTP 酶的调节因子:表征 RhoGDI 在肥大细胞释放促炎介质中的作用
- 批准号:
475576 - 财政年份:2022
- 资助金额:
$ 77.29万 - 项目类别:
Studentship Programs
Human secreted IgD: structure, interactions and mechanisms in allergic inflammation and asthma
人类分泌的 IgD:过敏性炎症和哮喘的结构、相互作用和机制
- 批准号:
MR/V010557/1 - 财政年份:2021
- 资助金额:
$ 77.29万 - 项目类别:
Research Grant
The impact of exposure to allergic inflammation on esophageal carcinogenesis
接触过敏性炎症对食管癌发生的影响
- 批准号:
10308094 - 财政年份:2020
- 资助金额:
$ 77.29万 - 项目类别:
The impact of exposure to allergic inflammation on esophageal carcinogenesis
接触过敏性炎症对食管癌发生的影响
- 批准号:
10112399 - 财政年份:2020
- 资助金额:
$ 77.29万 - 项目类别:
Foxp3+ regulatory T cell-dependent treatment of allergic inflammation by glucocorticoids
Foxp3 调节性 T 细胞依赖性糖皮质激素治疗过敏性炎症
- 批准号:
10447598 - 财政年份:2020
- 资助金额:
$ 77.29万 - 项目类别:
Foxp3+ regulatory T cell-dependent treatment of allergic inflammation by glucocorticoids
Foxp3 调节性 T 细胞依赖性糖皮质激素治疗过敏性炎症
- 批准号:
10218031 - 财政年份:2020
- 资助金额:
$ 77.29万 - 项目类别: