Project 3: Myeloid-lymphoid cell crosstalk in HNSCC therapy

项目 3:HNSCC 治疗中的骨髓-淋巴细胞串扰

基本信息

  • 批准号:
    10478901
  • 负责人:
  • 金额:
    $ 45.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-19 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Some head and neck squamous cell carcinoma (HNSCC) patients see pronounced clinical responses with immunotherapeutic intervention. These successes demonstrate the power of therapeutically (re-)activating antitumor T cells to control cancer, but are insufficient, considering the many more patients who do not experience clinical benefit when provided the same treatments. Increasing evidence shows two main barriers to immunotherapy’s success against HNSCC: (i) the tumor’s often poor antigenicity, which limits the generation of antitumor immunity, (ii) suppressive mechanisms that enforce immune tolerance within tumors. This P01’s goal is to address these two barriers: Projects 1 and 2 aim to identify ways that increase HNSCC antigenicity; this Project aims to direct enhanced antigenicity into a successful antitumor immune response. To this end, we will harness myeloid cell populations and their crosstalk with T cells. When considering myeloid cells, we are particularly interested in tumor-infiltrating dendritic cell (DC) populations, since they can present tumor-antigen to T cells and license the execution of T cell-mediated tumor control. We will initially assess three drugs, which we carefully chose based on their use in the clinic, their relevance to the other Projects, our initial data, and their ability to target multiple tumor-associated components. Namely, we will study: (1) 5’azacytidine since it augments tumor cell antigenicity in HNSCC patients and mice (see also Project 1); (2) anti-PD-1 mAb since it can activate T cells to produce key antitumor cytokines such as IFN-gamma and is efficacious in some HNSCC patients; (3) agonistic anti-CD40 mAb since it can induce a DC subset to produce the effector cytokine IL-12, which fosters antitumor T cell activity. Therefore, these drugs may be rationally combined to promote tumor control by targeting tumor cells, adaptive and innate immune cells simultaneously. We will also analyze other drugs during the 5-year project, based in part on findings from Projects 1 and 2. To define drug effects on myeloid⟷lymphoid cell crosstalk, we will leverage an ongoing clinical trial and animal models that recapitulate key features of the human disease. We will also use two complementary single cell resolution approaches: single cell RNA sequencing (scRNAseq) and single cell imaging (scIMAG). scRNAseq will provide an unbiased view of drug-induced immune changes in human and mouse lesions, and permit comparison across species to facilitate HNSCC translational research. scIMAG will provide information about drug-induced immune responses over time and within the geographical context of the tumor. We hypothesize that these approaches can identify mechanisms of drug-induced myeloid⟷lymphoid cell crosstalk, which are causally linked to HNSCC control and can be harnessed for therapy. We should be well positioned to perform the proposed work, having experience with studying immune cells and immunotherapy drugs, and having validated the tools that will be exploited in this project. Also, we have assembled a team of experts who will contribute to the project by providing key expertise in HNSCC immunotherapy, cell profiling, imaging, and statistics.
项目总结

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 }}

Mikael PITTET其他文献

Mikael PITTET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('Mikael PITTET', 18)}}的其他基金

Project 3: Myeloid-lymphoid cell crosstalk in HNSCC therapy
项目 3:HNSCC 治疗中的骨髓-淋巴细胞串扰
  • 批准号:
    10251171
  • 财政年份:
    2019
  • 资助金额:
    $ 45.53万
  • 项目类别:
Project 3: Myeloid-lymphoid cell crosstalk in HNSCC therapy
项目 3:HNSCC 治疗中的骨髓-淋巴细胞串扰
  • 批准号:
    10020927
  • 财政年份:
    2019
  • 资助金额:
    $ 45.53万
  • 项目类别:
Imaging endogenously produced tumor derived micro vesicles
内源性产生的肿瘤衍生微泡的成像
  • 批准号:
    8974820
  • 财政年份:
    2014
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    8579869
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    8370505
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    8077662
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    8035646
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    9416059
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    8765711
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:
In vivo behavior of monocytes in resting and inflammatory conditions
单核细胞在静息和炎症条件下的体内行为
  • 批准号:
    8196963
  • 财政年份:
    2010
  • 资助金额:
    $ 45.53万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 45.53万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了