The immune system plays a critical role in protecting the body from disease. However, in the context of cancer, the immune system becomes ineffective at recognizing and eliminating tumor cells. One important and often overlooked reason for this failure is that tumors pose not only biological but also physical challenges. As tumors grow, they generate crowding and pressure that physically squeeze nearby cells and disrupt how they function. With brain tumors, the skull limits how much the tissue can expand and amplifies these forces. This Faculty Early Career Development Program (CAREER) project investigates how these physical forces interfere with the ability of immune cells to find and destroy cancer cells, ultimately allowing tumors to grow unchecked. By uncovering how mechanical forces disrupt the immune system, this work addresses a fundamental gap in understanding how biology and physics interact in human health. The outcomes have broad implications for improving our understanding of cancer and immunity, guiding the design of new therapies, and advancing national priorities in biotechnology, health, and biomedical innovation. The project also includes integrated educational and training programs that engage students across multiple levels, providing research experiences and fostering multidisciplinary skills. These efforts will help prepare a capable workforce to address complex biomedical challenges. This research will establish fundamental principles of how compressive mechanical forces regulate immune cell fate and function in the tumor microenvironment. The central hypothesis is that growth-induced compressive forces directly impair the ability of anti-tumor immune cells to recognize and eliminate cancer cells. To test this, the project will combine engineered model systems spanning multiple scales, including cellular systems, organotypic brain models, and animal models of disease. Mechanical compression mimicking tumor growth will be precisely applied wh