AN ANALYSIS OF T-CELL-RECEPTOR VARIABLE-REGION GENES IN TUMOR-INFILTRATING LYMPHOCYTES WITHIN MALIGNANT-TUMORS

Expression of T-cell-receptor (TCR) V-alpha and V-beta genes in tumor-infiltrating lymphocytes (TILs) of 29 patients, 15 melanomas and 14 malignant glial tumors (glioma and medulloblastoma), was investigated. The identification and propagation of T cells with anti-tumor reactivity is crucial to the understanding of the human immune response to tumors, which may possibly be useful in the successful implementation of adoptive immunotherapy against cancer. Despite clinical evidence that a more favorable prognosis is associated with the degree of lymphocyte infiltration within a tumor, the actual role of TIL remains uncertain. In order to address this question, we examined the diversity of the RNA transcripts of TCR genes in TILs within 29 specimens obtained at surgery. Using the polymerase-chain-reaction (PCR) method and primers for 18 different human TCR V-alpha and 21 V-beta families to analyze TCR V-(D)-J-C gene rearrangements, we detected a limited expression of TCR variable-region Va genes of TILs. TCR V-beta gene rearrangements were more diverse than those for V-alpha. In addition to restricted usage of TCR V-alpha genes, preferential expression of V-alpha 7 genes was found in 20 out of 29 cases (69%). Predominant usage of V-alpha 7 genes was more remarkable in melanoma TILs (14/15) than in glial tumor TILs (6/14). These findings were also confirmed by Southern blot analysis with oligonucleotide probes for the constant (C) region of TCR-alpha and beta-chains. We suspect that some specific T-cell populations may be directed to antigenic determinants in melanoma cells.