[Comparative analysis of the immune response in a case of primary regressive melanoma followed by gastric metastasis].

The theory of immunosurveillance against cancer has been an extensively 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 have selected a study model, namely spontaneously regressive melanoma. A primary cutaneous lesion was investigated. T cell repertoire analysis showed the in situ amplification of at least two tumor infiltrating lymphocyte (TILs) expressing the V beta 13 and V beta 16 variable TCR gene segments respectively. The two clones were precisely characterized by sequence of the TCR beta chain junctional region. Further functional study demonstrated that both lymphocytes displayed a selective cytotoxic activity against autologous tumor cells. The V beta 16+ cells, predominant in vivo, were shown to be closely opposed to the melanoma cells. Together, these studies demonstrated the existence of a local adaptative immune response associated to tumor regression, thus strongly supporting the validity of the immunosurveillance concept. A gastric metastasis which occurred three years after the primary lesion has been studied here. Overexpression of the V beta 13 and V beta 16 TCR segments was no longer detected by direct PCR analysis in situ. Sequencing transcripts from V beta 13+ and V beta 16+ TILs confirmed that the two CTLs, identified in the primary lesions, were not represented with high frequency. The V beta 13+ cell was however shown to be present while the V beta 16+ CTL was not detected. Yet, characterization of a tumor cell line derived from the gastric site indicated that the peptidic antigen(s) which induced the initially successfully immune response was still expressed. The present data illustrate that it has become possible to perform very precise analysis of local immune responses during cancer development. Such an improvement together with the recently initiated molecular characterization of tumor associated peptidic antigens, should provide the basis for improved strategies of cancer immunotherapy.