Dynamic analysis of tumor infiltration and rejection by CTLs

Data was obtained on the infiltration and destruction of solid tumors by cytotoxic T lymphocytes (CTLs).

Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8+ CTLs, which infiltrate solid tumors, recognize tumor antigens and kill tumor cells. We used a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instant velocities. When the tumors express cognate antigens the CTLs are arrested in close contact to tumor cells. In regions of the tumors where the tumor cells are dead, CTL motility resumes, using apparently non-guided trajectories, or following collagen fibers or blood vessels. Strikingly, CTLs followed blood vessels for extended lengths, adopting an elongated morphology. CTLs also infiltrated tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the CTL cognate antigen, we observe peripheral infiltration by CTLs, but the lymphocytes neither stop moving, nor kill tumor cells or infiltrate tumors deeply. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and the depth of tumor infiltration. This work is currently submitted for publication.

• molecule type
• CD8

• cell type
• cytotoxic T lymphocyte,
• tumor cell

created over 16 years ago (2 March 2009)    last modified over 12 years ago (28 August 2012)   [ RDF ]   [ RelFinder ]