Defining the Role of CD26 in Checkpoint Blockaded Induced Tumor Immunity

定义 CD26 在检查点阻断诱导肿瘤免疫中的作用

基本信息

  • 批准号:
    10621564
  • 负责人:
  • 金额:
    $ 8.37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-13 至 2023-04-30
  • 项目状态:
    已结题

项目摘要

Abstract: The objective of this MPI R21 is to support an important discovery found by this basic T cell immunologist and immune-therapist (Dr. Chrystal Paulos) and surgeon and scientist (Dr. David Neskey) research team in a Phase II clinical trial (NCT03021993) in patients with oral cavity squamous cell carcinoma (OCC). These patients were treated with Nivolumab as a novel neoadjuvant pre-surgical therapy at our institution (Hollings Cancer Center). Our unpublished work reveals that a remarkable 44% of patients responded to this therapy via pathological score. While promising, 56% of the patients remain unresponsive to this treatment. Our new data reveals that responders express higher CD26 (co-stimulatory molecule with enzyme activity) on tumor- infiltrating lymphocytes (TILs), while CD26 was far lower on TILs from non-responders. These data suggest that CD26 plays a critical role in the function and migration of antitumor T cells to the oppressive tumor microenvironment in patients responsive to PD-1 therapy. We propose to gain insight into CD26-expressing T cells in the tumor, positing that the enzymatic CD26 activity augments the function, migration and antitumor activity of human TILs (Aim 1) and that targeting this pathway can improve cancer immunotherapy in non- responders: an idea we will explore in Aim 2, using our highly clinically relevant OCC tumor models. Overall, the proposed research is expected to demonstrate that manipulation of the CD26 pathway may sufficiently induce durable immunity against advanced OCC tumors and rescue patients non-responsive to PD-1 therapy.
文摘:

项目成果

期刊论文数量(1)
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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Chrystal Mary Paulos其他文献

Chrystal Mary Paulos的其他文献

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{{ truncateString('Chrystal Mary Paulos', 18)}}的其他基金

Mechanisms of Durable Antitumor Immunity Mediated by PI3K-targeted T cells
PI3K 靶向 T 细胞介导的持久抗肿瘤免疫机制
  • 批准号:
    10682190
  • 财政年份:
    2023
  • 资助金额:
    $ 8.37万
  • 项目类别:
Mechanisms of durable antitumor immunity via CD26hiCD4+ T cells
CD26hiCD4 T 细胞持久抗肿瘤免疫的机制
  • 批准号:
    10227546
  • 财政年份:
    2016
  • 资助金额:
    $ 8.37万
  • 项目类别:
Costimulatory mechanisms of antitumor Th17 cell immunity
抗肿瘤Th17细胞免疫的共刺激机制
  • 批准号:
    8847568
  • 财政年份:
    2013
  • 资助金额:
    $ 8.37万
  • 项目类别:
Costimulatory mechanisms of antitumor Th17 cell immunity
抗肿瘤Th17细胞免疫的共刺激机制
  • 批准号:
    9042984
  • 财政年份:
    2013
  • 资助金额:
    $ 8.37万
  • 项目类别:
Costimulatory mechanisms of antitumor Th17 cell immunity
抗肿瘤Th17细胞免疫的共刺激机制
  • 批准号:
    8685915
  • 财政年份:
    2013
  • 资助金额:
    $ 8.37万
  • 项目类别:
Costimulatory mechanisms of antitumor Th17 cell immunity
抗肿瘤Th17细胞免疫的共刺激机制
  • 批准号:
    9260847
  • 财政年份:
    2013
  • 资助金额:
    $ 8.37万
  • 项目类别:
Costimulatory mechanisms of antitumor Th17 cell immunity
抗肿瘤Th17细胞免疫的共刺激机制
  • 批准号:
    8596277
  • 财政年份:
    2013
  • 资助金额:
    $ 8.37万
  • 项目类别:

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