Making and circumventing tolerance to cancer.

The interactions between cancer and immune cells are complex. Even though the mutations that cause cancer can create new antigens that are potentially "visible" to T cells, in most experimental model systems the growth of tumors is accompanied by induction of T-cell tolerance towards the tumor. How tolerance to tumors is induced and how tolerance can be broken by immunotherapy have been a main focus in cancer immunology. Here, we discuss experimental models used in cancer immunology. We argue that, while it is obviously easy for tumors to induce tolerance, it should be as easy to circumvent tolerance by the adoptive transfer of tumor-antigen-reactive T cells. Effective adoptive T-cell therapy has become feasible by methods to identify TCR against tumor-associated (self-) antigens with high affinity and to graft a new antigen specificity to patients' T cells by TCR gene transfer.