Tumor Microenvironment

UWCCC肿瘤微环境计划摘要 联合领导人：帕梅拉·克里格和乔什·朗 项目摘要/摘要 癌症不是孤立发展的，而是在反应间质和免疫细胞的复杂环境中发展起来的。 构成了肿瘤的微环境。肿瘤相关成纤维细胞之间的动态相互作用 (CAF)、免疫细胞和细胞外基质(ECM)已被证明可促进肿瘤生长，启动 转移级联作用，并促进多种癌症的治疗耐药。治疗方面的进展 确认了靶向肿瘤微环境的不可思议的潜力，但也发现了意想不到的 反应的异质性和不同的抗性机制。因此，这是肿瘤的使命 微环境(TM)计划，以识别在肿瘤发生和发展过程中发生的微环境变化 分析肿瘤细胞和微环境成分之间的相互作用如何影响肿瘤的形成， 生长、转移和对治疗的反应。通过这些研究努力，TM计划的成员是 确定新的生物标记物和治疗方法。为了实现这些目标，TM计划促进了 来自校园14个系的33名成员之间的合作，其中包括生物学家， 生物工程师和临床医生。TM计划正在追求三个具体目标，重点是UWCCC 优先针对乳腺癌和前列腺癌，因为它们在我们的流域很高： 目的1：分析细胞外基质在肿瘤发生和转移中的作用。 目的2：分析肿瘤发生和发展过程中肿瘤微环境内多细胞间的相互作用 转移。 目的3：探讨调节治疗反应的肿瘤微环境中的生物相互作用 和抵抗。 TM成员得到了NCI资金350万美元的直接成本和510万美元的额外直接成本的支持 在上一个预算年度提供了同行评审的癌症相关支持，并在696例癌症方面取得了很高的成效- 在上一个赠款周期期间出版了相关出版物。在这些出版物中，17%是内部出版的 方案协作和32%是方案间协作，比上一次有所增加 周而复始。仅在2021年，就有近一半的出版物是与其他机构合作的。

UWCCC Tumor Microenvironment Program Summary Co-Leaders: Pamela Kreeger and Josh Lang PROJECT SUMMARY/ABSTRACT Cancer does not develop in isolation, evolving instead in a complex milieu of reactive stroma and immune cells that constitute the tumor microenvironment. Dynamic interactions between cancer-associated fibroblasts (CAFs), immune cells, and the extracellular matrix (ECM) have been shown to enhance tumor growth, initiate the metastatic cascade, and promote treatment resistance in a variety of cancers. Therapeutic advances have confirmed the incredible potential of targeting the tumor microenvironment but also identified unexpected heterogeneity in response and diverse mechanisms of resistance. Therefore, it is the mission of the Tumor Microenvironment (TM) Program to identify microenvironmental changes that occur during tumorigenesis and analyze how the interactions between the tumor cell and microenvironmental components affect tumor formation, growth, metastasis, and response to therapies. Through these research efforts, members of the TM program are identifying new biomarkers and therapeutic approaches. To accomplish these goals, the TM program fosters collaborations between its 33 members from 14 departments across campus, which include biologists, bioengineers, and clinicians. The TM program is pursuing three Specific Aims, with an emphasis on UWCCC priority targets breast and prostate cancer due to their high prevalence in our catchment: Aim 1: Dissect the role of the extracellular matrix in tumor initiation and metastasis. Aim 2: Analyze multi-cellular interactions within the tumor microenvironment during tumor initiation and metastasis. Aim 3: Interrogate the biological interactions in the tumor microenvironment that mediate treatment response and resistance. TM members were supported by $3.5 million direct costs in NCI funding and $5.1 million direct costs in additional peer-reviewed cancer-related support in the last budget year, and were highly productive with 696 cancer- relevant publications during the course of the last grant cycle. Of these publications, 17% were intra- programmatic collaborations and 32% were inter-programmatic collaborations, increases from the previous cycle. In the year 2021 alone, nearly half of publications were collaborative with other institutions.