Early investigation of the role of desmoplastic fibrosis in cutaneous squamous cell carcinoma
促结缔组织增生性纤维化在皮肤鳞状细胞癌中作用的早期研究
基本信息
- 批准号:10418738
- 负责人:
- 金额:$ 8.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-04 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAgeAmerican Joint Committee on CancerAreaBand CellBiochemicalBioinformaticsBiologicalBlood VesselsCell CommunicationCellsCessation of lifeClinicalCollagenCommunity Clinical Oncology ProgramDataDeath RateDepositionDesmoplasticDiseaseExclusionExpression ProfilingFDA approvedFailureFibrosisGenderGene ExpressionGene Expression ProfilingGenesHistologicImageImmuneImmune systemImmunofluorescence ImmunologicImmunohistochemistryImmunooncologyImmunotherapyImpotenceInfiltrationInvestigationKnowledgeLaboratoriesLinkLymphaticLymphocyteLymphovascularMalignant NeoplasmsMeasuresMediatingModelingMorbidity - disease rateNeoplasm MetastasisOutcomePathway interactionsPatientsPatternPharmaceutical PreparationsPlayPopulationPrognostic FactorProteinsRecurrenceResearchResearch PersonnelResistanceRiskRoleSlideStructureSystemT cell responseT-LymphocyteT-Lymphocyte SubsetsTestingTissue MicroarrayTissue SampleTissue-Specific Gene ExpressionTumor EscapeTumor stageTumor-infiltrating immune cellsWorkanti-PD-1cancer cellcytotoxicinnovationinsightinterestlymphatic vesselmRNA Expressionmelanomamortalitynano-stringneoplastic cellnovelpreventprotein expressionresponseskin squamous cell carcinomatumor
项目摘要
Project Summary/Abstract
The only FDA-approved treatment for advanced cutaneous squamous cell carcinoma (CSCC) (cemiplimab, an
immunotherapy drug that helps the immune system kill cancer cells) is only effective in 50% of patients. There
are no known predictors of immunotherapy failure in CSCC. Addressing this gap in knowledge regarding why
immunotherapy often fails is central to our ability to further decrease morbidity and mortality from
CSCC and other cancers in which immunotherapy plays a major role. Desmoplasia (deposition of abnormal
collagen in the area around a tumor) is an independent prognostic factor in CSCC associated with
death. However, systems for quantifying desmoplasia have not been developed and how it causes poor
outcomes in CSCC has not been studied. Our laboratory seeks to determine why desmoplasia is linked to
poor outcomes. We have developed the first system for quantifying desmoplasia. Our early data indicate
prominent desmoplasia is associated with a markedly lower 5-year cure rate (60%) as compared to when there
is no desmoplasia (90%). Our data also indicate that when immune cells do not infiltrate tumors, cure rate is
worse (40% vs. 75% when immune T cells are present). Finally, we have noted in cases of prominent
desmoplasia a pattern whereby immune cells are sequestered away from the tumor by the desmoplastic
region. If this is true, desmoplasia may be a major mechanism accounting for failure of immunotherapy since
this therapy cannot work without T cell contact with tumor cells. We propose to verify that desmoplasia is
associated with metastasis and death as well as decreased T cell contact with tumor, and to identify genes that
may be involved in the desmoplastic/fibrotic pathway and T cell exclusion. If the proposed studies show that
desmoplasia is linked to T cell exclusion from tumor, further studies aimed at combatting desmoplasia may be
enable greater efficacy of immunotherapy.
项目总结/摘要
FDA批准的唯一一种治疗晚期皮肤鳞状细胞癌(CSCC)的药物(cemiplimab,
免疫治疗药物,帮助免疫系统杀死癌细胞)只对50%的患者有效。那里
没有已知的CSCC免疫治疗失败的预测因子。解决这一知识差距,
免疫治疗往往失败是我们能够进一步降低发病率和死亡率的核心,
CSCC和免疫疗法发挥主要作用的其他癌症。结缔组织增生(异常结缔组织沉积)
胶原蛋白)是CSCC的独立预后因素,
死亡然而,尚未开发出量化结缔组织增生的系统以及它如何导致不良反应。
尚未研究CSCC的结局。我们的实验室试图确定为什么结缔组织增生与
可怜的结果。我们已经开发了第一个定量结缔组织增生的系统。我们的早期数据显示
突出的结缔组织增生与明显较低的5年治愈率(60%)相关,
无结缔组织增生(90%)。我们的数据还表明,当免疫细胞不浸润肿瘤时,
更糟(40%对75%,当免疫T细胞存在时)。最后,我们注意到,
结缔组织增生是一种免疫细胞被结缔组织增生性结缔组织隔离远离肿瘤的模式。
地区如果这是真的,结缔组织增生可能是免疫治疗失败的主要机制,
如果T细胞不与肿瘤细胞接触,这种疗法就不能起作用。我们建议证实结缔组织增生是
与转移和死亡以及T细胞与肿瘤接触减少相关的基因,并鉴定
可能参与促结缔组织增生/纤维化途径和T细胞排斥。如果拟议的研究表明,
结缔组织增生与T细胞从肿瘤中排除有关,进一步的研究旨在对抗结缔组织增生,
提高免疫治疗的效果。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Chrysalyne Delling Schmults其他文献
Chrysalyne Delling Schmults的其他文献
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{{ truncateString('Chrysalyne Delling Schmults', 18)}}的其他基金
Early investigation of the role of desmoplastic fibrosis in cutaneous squamous cell carcinoma
促结缔组织增生性纤维化在皮肤鳞状细胞癌中作用的早期研究
- 批准号:
10202093 - 财政年份:2021
- 资助金额:
$ 8.95万 - 项目类别:
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