Project description:Immune cell interactions with tumor cells are critical for cancer therapeutic response, but it is unclear whether T cells take a direct or random path into a tumor. We performed 3D, long-term imaging of zebrafish melanomas and found that CD8+ T cells localize to craters on the tumor surface. Craters are the primary site of CD8 T cells accumulation and activation following CpG oligonucleotide injection, TLR agonists that elicit an immune response, or systemic TGF-β inhibition. Human melanomas exhibit craters at the tumor surface and in perivascular spaces where they harbor dysfunctional, proliferative CD8+ T cells. In both zebrafish and human tumors, crater size and number positively correlate with CD8+ T cell infiltration. These results identify craters as hubs that provide a direct path for CD8+ T cells into tumors.
Project description:Immune cell interactions with tumor cells are critical for cancer therapeutic response, but it is unclear whether T cells take a direct or random path into a tumor. We performed 3D, long-term imaging of zebrafish melanomas and found that CD8+ T cells localize to craters on the tumor surface. Craters are the primary site of CD8 T cells accumulation and activation following CpG oligonucleotide injection, TLR agonists that elicit an immune response, or systemic TGF-β inhibition. Human melanomas exhibit craters at the tumor surface and in perivascular spaces where they harbor dysfunctional, proliferative CD8+ T cells. In both zebrafish and human tumors, crater size and number positively correlate with CD8+ T cell infiltration. These results identify craters as hubs that provide a direct path for CD8+ T cells into tumors.
