权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Use of focused ultrasound to increase melanoma immunogenicity and inhibit tumor-induced T cell tolerance

使用聚焦超声增加黑色素瘤免疫原性并抑制肿瘤诱导的 T 细胞耐受

基本信息

批准号：
10365967
负责人：
Chandan Guha
金额：
$ 37.44万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
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：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10365967
关键词：
Adaptive Immune System Address Adverse effects Adverse reactions Agonist Antibodies Antigen-Presenting Cells Antigens Antitumor Response Autologous Autophagocytosis Behavior CCL4 gene CTLA4 gene Cancer Vaccines Cell Death Cell Maturation Cell surface Cellular Stress Clinic Data Dendritic Cells Dendritic cell activation Distal EGR2 gene Focused Ultrasound Focused Ultrasound Therapy Generations Goals Immune Immune Tolerance Immune checkpoint inhibitor Immune response Immunotherapeutic agent Immunotherapy In Situ In Vitro Melanoma Cell Melanoma Vaccine Metastatic Neoplasm to the Lung Modeling Molecular Chaperones Monitor Mus Neoplasm Metastasis Pathway interactions Population Precancerous melanosis Primary Neoplasm Protocols documentation Recurrence Specificity Stress Suppressor-Effector T-Lymphocytes T cell response T-Cell Activation T-Lymphocyte Therapeutic Agents Time Toxic effect Translating Tumor Antigens Ultrasonic Therapy anti-melanoma immunity antigen-specific T cells cancer immunotherapy combinatorial cost effective cytokine design exosome immune checkpoint blockade immunogenic immunogenic cell death immunogenicity immunoregulation improved in situ cancer vaccine in vivo melanoma mouse model neoplasm immunotherapy neoplastic cell novel novel therapeutic intervention prevent programmed cell death ligand 1 programmed cell death protein 1 programs recruit response transcription factor tumor tumor growth tumor microenvironment tumor-immune system interactions

项目摘要

Immunosuppressive mechanisms in the tumor microenvironment promote tumor growth by preventing the adaptive immune system from mounting effective antitumor responses. One of the main consequences of the immunosuppressive tumor microenvironment is the induction of tumor antigen-specific T cell tolerance. Overcoming such blockade has remained a major challenge in cancer immunotherapy. Our data show that thermic and physical stress induced by low-intensity focused ultrasound (LOFU) prevents the induction of tumor- antigen specific T cell tolerance and, in combination with ablative therapy, results in improved control of primary melanoma, reduces local recurrence and markedly decreases the occurrence of pulmonary metastases. This represents a new therapeutic approach that by acting locally on tumor cells has the potential to inhibit the establishment of tumor-antigen specific induced T cell tolerance. In this application, our goal is to understand the mechanisms that induce enhanced immunogenic melanoma cell death after LOFU-treatment, determine the potential of using LOFU+ablation as an in-situ melanoma vaccine and finally study whether LOFU can increase efficiency and reduced toxicity when used in combination with checkpoint inhibitors.

肿瘤微环境中的免疫抑制机制通过阻止肿瘤细胞凋亡来促进肿瘤生长