T-CELL RECEPTOR REPERTOIRE IN NEUROBLASTOMA PATIENTS

Spontaneous regression of widespread lesions is a characteristic featu re of neuroblastoma. One may postulate that the immune response contri butes to these clinical regressions. Accordingly, we studied the T-cel l receptor (TCR) repertoire of tumor-infiltrating lymphocytes in eight neuroblastoma tumors. The expression of 29 V alpha and 24 V beta gene segment subfamily specificities was analyzed by PCR and compared by c omputerized densitometry of Southern blots to values obtained in the b lood. Overall, the TCR repertoire of these eight patients was diverse, with virtually all V alpha and V beta specificities expressed. Noneth eless, four of these patients showed V beta 2 gene segment subfamily o verexpression in the tumor corresponding to local expansion of polyclo nal T-cell subpopulations. In one patient, this expansion could be due to local secretion of superantigenic activity, as suggested by the sp ecific stimulation of murine T cells expressing a human V beta 2 chain by supernatant of the corresponding neuroblastoma cell line. In addit ion, high-resolution analysis of the TCR beta transcript complementari ty-determining region 3 sizes identified three patients (of six studie d) with marked clonal T-cell expansion in the tumor not seen in the bl ood. The specific expression of several dominant clonotypes in the tum or may be related to the recognition of neuroblastomas-specific antige ns in these patients. Together, these results on the TCR repertoire ex pressed in vivo may lead to the characterization of putative immune re sponse mechanisms (i.e., antigen- or superantigen-driven stimulation) which participate in tumor regression.