Fig. 4.

Model of tumor antigen-specific T cell accumulation in tumor-draining lymph nodes.

Lymphatics draining tumors deliver T cells (effector T cells – Teff and effector memory T cells (Tem) along with dendritic cells (DC) cross-presenting tumor antigens to the draining lymph node. Other sites in the lymphatic drainage basin may also provide T cells and DC cross-presenting irrelevant antigens. In addition, naïve T cells (Tnaive) and central memory T cells (Tcm) can directly enter the lymph node via high endothelial venules. Within the lymph node T cells that fail to find their cognate antigen (blue), randomly screen antigen presenting cells under the competing influence of chemokines such as CCL7 and S1P, which directs lymphocyte exit. Tumor-specific T cells (red) may arrest on meeting their cognate antigen, and adhesion molecule interactions will overcome exit signals to permit the cells to accumulate and potentially proliferate. Over time, these cells may exceed the available antigen presenting capacity and respond to exit signals. Thus, the transit time of tumor-antigen specific cells may be significantly slower than non-specific T cells.