DIRECT EVIDENCE TO SUPPORT THE IMMUNOSURVEILLANCE CONCEPT IN A HUMAN REGRESSIVE MELANOMA

The concept of immunosurveillance against cancer has been an extensive ly debated question over the last decades. Multiple indirect arguments have supported the view that the immune system may control, at least in certain cases, malignant cell growth while direct demonstration is still lacking in the human. In an attempt to address this issue, we ha ve selected a study model, namely spontaneously regressive melanoma. I n previous series of experiments, the variability of T cell receptors (TCRs) in the lymphocytes infiltrating a regressive tumor lesion was i nvestigated. Results demonstrated that clonal T cell populations, prec isely defined through their V-D-J junctional sequences, were amplified in situ. One clone was predominant, expressing the V beta 16 variable gene segment. A specific anti-V beta 16 TCR mAb was generated here to purify and functionally characterize the corresponding cells. A tumor -infiltrating lymphocyte-derived V beta 16(+) T cell line was develope d using this reagent. These in vitro cultured cells mere found to expr ess the in vivo predominant TCR sequence exclusively and to display an HLA-B14-restricted cytotoxic activity against the autologous tumor ce lls. Immunohistochemical experiments, performed with the anti-V beta 1 6 mAb, showed that the corresponding CTLs are present in the tumor are a, some of them being closely opposed to the melanoma cells. Together, these studies demonstrate the existence of a local adaptive immune re sponse clinically associated to tumor regression, thus strongly suppor ting the validity of the immunosurveillance concept in certain human t umors.