Rethinking EAE pathogenesis

Vaccination with tumor antigens causes tumor regression in some melanoma patients despite negligible expansion of vaccine-specific T cells. Vaccination may instead result in the expansion of T cells specific for tumor antigens not contained in the vaccine, thus facilitating tumor regression, according to two articles from Pierre Coulie and colleagues on pages 241 and 249. 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 antigens sometimes causes regression without expanding large numbers of vaccine-specific killer T cells. Pierre Coulie’s group studied the specificity of antitumor T cell responses in patients vaccinated with a tumor antigen called MAGE-3. In one patient whose tumors regressed after vaccination, the authors found that T cells specific for nonvaccine tumor antigens became detectable or expanded from their prevaccine frequencies. Vaccine-specific T cells became detectable but remained at low frequency. Thus, reinvigoration of existing tumorspecific T cells and activation of new T cells after vaccination does not require large numbers of vaccine-specific T cells. Although the mechanism underlying this phenomenon Tumor-specific T cells (red) infiltrate a tumor after vaccination.