Introduction: immune recognition of tumour cells

In the late 1980s it became clear that cancer cells develop by multiple genetic alterations (reviewed in Weinberg, 1989; Bishop, 1991). These alterations include activation of proto-oncogenes as well as inactivation of tumour suppressor genes. Proto-oncogenes, more commonly called oncogenes, exert important functions in cell proliferation and differentiation and their activity is usually tightly controlled to ensure a minimal risk of inappropriate activity. Activation of oncogenes in animal and human tumours may occur through several mechanisms including amplification, elevated expression and point mutations. These genetic alterations usually result in an altered activity of the oncogene-encoded protein and this contributes to uncontrolled proliferation.

In the light of the crucial role that HLA class I antigens play in the interaction of altered self antigens or viral antigens with CTLs (see Chapter 1), one would expect that antigens specifically present in tumours are presented by HLA class I molecules. Such antigens might be viral antigens in the case of virally induced tumours or altered self proteins in the case of tumours induced by xenobiotics like carcinogens or radiation. In numerous animal and human tumours, mutations in oncogenes have been shown to be responsible for the tumorigenic properties of the tumour cell. These mutations are potential targets for recognition by the immune system of the host. Candidate oncogene and tumour suppressor proteins are ras and p53 proteins, respectively; these can be activated by various mutations and are involved in many forms of human cancer (reviewed in Bos, 1989; Levine, Momand & Finlay, 1991).