Probing microenvironmental immunobiology to support understanding of novel anti-cancer biotherapeutic interventions in MSS colorectal cancer

本研究将探讨结直肠癌患者的抗肿瘤免疫调节。关注对当前免疫治疗方法反应不良的低突变患者群体，它将使用一系列尖端技术来探索干预的关键途径的免疫生物学。这些研究将使用“多模式”方法，包括多重免疫荧光和空间转录组学，以及创新的离体和体内模型，以探索潜在的疾病机制和微环境免疫生物学。伯明翰大学（UoB）和Astra Zeneca （AZ）团队之间的密切合作将使学生能够利用针对三种特定肿瘤途径的候选治疗性抗体资产。该奖学金将提供组织微环境生物学方面的优秀培训，使学生能够最大限度地利用大华大学和阿斯利康大学的优秀机会，包括数字病理分析、组织切片模型和多模态数据集成。该结果可能有助于确定最有可能对AZ免疫肿瘤学资产作出反应的患者亚组，确定潜在的分层方法和预测性生物标志物，并为免疫肿瘤学联合方法提供信息。学生应该完成他/她的学业，具有一系列具有战略意义的关键实验、分析和科学技能，理想定位于进一步探索学术界或工业界的治疗发展。

This studentship will explore regulation of anti-tumour immunity in the setting of colorectal cancer. Focussing on low mutation patient groups poorly responsive to current immunotherapy approaches, it will use a range of cutting-edge technologies to probe the immunobiology of key pathways for intervention. These studies, will use a 'multimodal' approach involving multiplex immunofluorescence and spatial transcriptomics, as well as innovative ex vivo and in vivo models, to explore underlying disease mechanisms and microenvironmental immunobiology. Close collaboration between the University of Birmingham (UoB) and Astra Zeneca (AZ) teams will enable the student to leverage candidate therapeutic antibody assets targeted at three specific tumour pathways. The studentship will provide an excellent training in tissue microenvironmental biology, allowing the student to maximise outstanding opportunities at UoB and AZ, including in digital pathology analyses, tissue slice models, and multimodal data integration. The results will likely help define patient subgroups most likely to response to AZ immuno-oncology assets, identify potential stratification approaches and predictive biomarkers, and inform immune-oncology combination approaches. The student should complete his/her studies with a range of strategically critical experimental and analytical and scientific skills, ideally positioned to further explore therapeutic development either in academia or industry.