Immunotherapy targeting negative immune checkpoints has emerged as a transformative approach in cancer treatment. In Colorectal Cancer, the tumor microenvironment plays a pivotal role in immune suppression, enabling tumor cells to evade immune surveillance. Key immune checkpoints, including PD-1, PD-L1, CTLA4, and Fas ligand, are critical in modulating these interactions, making them prime therapeutic targets.
The central hypothesis is that stromal cells directly influence T cell-mediated anti-tumor immunity in colorectal patients and offer novel therapeutic avenues including immunotherapy.
The aim of this project is to determine the expression patterns of key immune checkpoints in tumor and immune cells in CRC and explore the role of these checkpoints in immune suppression within the tumor microenvironment providing insights into how checkpoint blockade therapies can be optimized for CRC patients.
Objectives:
Isolate stromal and immune cells (T cells and macrophages) from fresh colorectal tumor resection samples in collaboration with Dr. Ryan’s team.
Characterize stromal cell surface markers and assess their pro- and anti-inflammatory molecule expression using flow cytometry and RT-PCR.
Examine how stromal cells modulate T cell and macrophage phenotypes through co-culture experiments.