ANALYSIS OF T-CELL-RECEPTOR VARIABLE GENE SEGMENT USAGE IN PERIPHERAL-BLOOD LYMPHOCYTES OF ADVANCED CANCER-PATIENTS

Advanced cancer patients generally display impaired T-cell immune functions. The underlying mechanisms are not well understood. The aim of this study was to analyze whether major alterations of TCR variable gene segment usage could be detected in the blood of these patients. Seventeen individuals with various malignancies were tested using PCR and a panel of V-gene-segment-sub-family-specific (ValphaI-w29/VbetaI-w24) oligonucleotide primers. The results indicate that these cancer patient lymphocytes expressed most Valpha and Vbeta sub-family specificities, similarly to the lymphocytes of healthy donors (n = 10). This suggests that immunodepression in advanced cancer patients is not related to major deletions in their T-cell repertoires. We also compared the mean relative expression of each V-sub-family specificity of patients and healthy donors by quantitative densitometric analysis. We found significant differences in 4 Vbeta specificities (and no Valpha). Our analysis identified unique T-cell sub-sets putatively involved in the mechanisms leading to immunodepression in advanced cancer patients. Alternatively, the observed differences in terms of Vbeta specificity expression may reflect the host response against the tumor.