Lymphoma monocyte crosstalk: mechanisms of chemo-immunotherapy resistance

淋巴瘤单核细胞串扰：化疗免疫治疗耐药机制

• 批准号: 9144324
• 负责人: Yi Lin
• 金额: $ 19.28万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-14 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9144324
• 关键词: Animal Model; Antigens; Autologous Dendritic Cells; Automobile Driving; B-Cell NonHodgkins Lymphoma; CD14 gene; Cancer Patient; Cancer Research Project; Cells; Cellular Stress; Clinic; Clinical; Clinical Trials; Data; Dendritic Cells; Development; Development Plans; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Ensure; Exhibits; Funding; Future; Goals; HSPB1 gene; Health; Hematologist; Immune; Immune System Diseases; Immune system; Immunity; Immunosuppression; Immunosuppressive Agents; Immunotherapy; In Vitro; Infection; Inflammatory; Iowa; K-Series Research Career Programs; K22 Award; Lymphoma; Malignant Neoplasms; Mayo Clinic Cancer Center; Mediating; Mediator of activation protein; Mentors; Methods; Modeling; Morbidity - disease rate; Natural Killer Cells; Non-Hodgkin' s Lymphoma; Outcome; Patients; Phase; Phenotype; Play; Research; Research Personnel; Resistance; Resources; Role; Testing; Tissues; Training; Translating; Translational Research; Tumor Immunity; Universities; Vaccine Therapy; Vaccines; Work; adaptive immunity; cancer therapy; cancer type; career; career development; chemotherapy; cytokine; cytotoxic; immune function; improved; in vitro Model; in vivo; innovation; killings; laboratory experience; monocyte; novel; personalized medicine; pre-clinical; programs; receptor; targeted treatment; therapy design; therapy development; therapy resistant; treatment response; tumor

 DESCRIPTION (provided by applicant): Dr. Yi Lin M.D. Ph.D. is currently a clinical hematologist at Mayo Clinic. Her long-term goal is to establish an independent academic career in translational research to identify mechanisms of tumor-mediated immune suppression, develop strategies to overcome this suppression, and test these strategies in early phase clinical trials. Her immediate goal is to generate data for a successful R01 application examining mechanisms of lymphoma-associated monocyte and tumor crosstalk that promote treatment resistance in lymphoma. Mayo Clinic has a strong cancer research program and a long track record of training successful translational and clinical researchers. Dr. Lin is supported by Mayo Clinic Cancer Center and the University of Iowa/Mayo Clinic Lymphoma SPORE to ensure adequate access to resources to complete the proposed project. Dr. Lin's K22 career development plan includes gaining competency in working with animal models and strengthening practical laboratory experience to establish an independently funded research program. In her current work, Dr. Lin has found that monocytes are commonly immune suppressive in many cancer types and contributes to aggressive disease and poor clinical outcome. Focusing on lymphoma as a tumor model, she has found that lymphoma-associated monocytes (LA-CD14) are not only immunosuppressive but also directly promote lymphoma resistance to chemotherapy. In this K22 proposal, Dr. Lin will examine mechanisms of LA-CD14 and lymphoma crosstalk that promote treatment resistance. This will be achieved through two specific aims: 1) Determine the mechanism of LA-CD14 mediated promotion of lymphoma resistance to chemotherapy. 2) Determine the mechanism of LA-CD14 mediated protection of lymphoma from anti-tumor immunity. Successful completion of this project will provide the foundational data for an R01 application to study specific strategies to re-sensitize lymphoma to chemo-immunotherapy. The NCI K22 award will provide critical support for Dr. Lin's transition from a mentored researcher to an independent investigator.

 描述（申请提供）：Yi Lin M.D.博士博士目前是梅奥诊所的临床血液学家。她的长期目标是在翻译研究中建立独立的学术职业，以确定肿瘤介导的免疫抑制的机制，制定克服这种抑制的策略，并在早期临床试验中测试这些策略。她的近期目标是生成成功的R01应用检查机制的淋巴瘤相关单核细胞和肿瘤串扰的数据，从而促进淋巴瘤的治疗耐药性。 Mayo Clinic拥有强大的癌症研究计划，并且是培训成功的转化和临床研究人员的悠久记录。 Lin博士得到了Mayo Clinic Cancer Center和爱荷华大学/Mayo诊所淋巴瘤孢子的支持，以确保足够的资源访问拟议项目。 Lin博士的K22职业发展计划包括获得与动物模型合作并增强实践实验室经验以建立独立资助的研究计划的能力。林博士在目前的工作中发现，单核细胞在许多癌症类型中通常是免疫抑制性的，并导致侵袭性疾病和临床结果不佳。她以淋巴瘤为肿瘤模型，发现与淋巴瘤相关的单核细胞（LA-CD14）不仅是免疫抑制作用，而且还直接促进了对化学疗法的抗淋巴瘤。在此K22提案中，Lin博士将检查LA-CD14和Crosstalk的LA-CD14和淋巴瘤的机制，这些机制促进了治疗耐药性。这将通过两个特定的目的来实现：1）确定LA-CD14介导的促进淋巴瘤对化学疗法的抗性的机理。 2）确定LA-CD14介导的淋巴瘤免受抗肿瘤免疫的保护的机理。该项目的成功完成将为R01应用提供基础数据，以研究重新敏感淋巴瘤对化学免疫疗法的特定策略。 NCI K22奖将为Lin博士从指导的研究人员到独立研究者的过渡提供重要的支持。