Advanced melanoma, the most deadly form of skin cancer, can be successfully treated in some cases by vaccinating patients with tumor proteins. How these vaccines work and why they are only effective in some patients remains unclear. Pierre Coulie and colleagues now show, in two articles in the January 17 issue of the Journal of Experimental Medicine, that these vaccines work by increasing the number of immune cells called killer T cells that can attack the tumor. In an unexpected finding, however, they discovered that that these cells mostly recognize tumor proteins that were not contained in the vaccine. Understanding the characteristics of the T cell populations that are expanded after vaccination may help in the development of more effective anti-tumor vaccines.

Tumor-specific T cells can be detected in the blood and the tumors of many melanoma patients, and yet these cells are unable to kill the tumor. What causes the impotence of these T cells is a mystery. Equally mysterious is why vaccination against tumor-specific proteins sometimes causes tumor regression without expanding large numbers of vaccine-specific killer T cells.

Pierre Coulie's group studied anti-tumor T cells in patients vaccinated with a tumor antigen called MAGE-3. In one patient whose tumor regressed after vaccination, the authors found significantly more T cells specific for non-vaccine tumor proteins than were detected before vaccination. Vaccine-specific T cells, on the other hand, became detectable but did not expand to large numbers. Thus, reinvigoration of existing tumor-specific T cells after vaccination did not require large numbers of vaccine-specific T cells.

Although it is not known how these tumor-specific cells get activated, Coulie thinks that the few T cells stimulated by the vaccine may change the local, suppressive environment of the tumor such that other T cells can snap out of their stupor and attack the tumor.

Contact: Nickey Henry
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Journal of Experimental Medicine