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 func tions. The underlying mechanisms are not well understood. The aim of t his study was to analyze whether major alterations of TCR variable gen e segment usage could be detected in the blood of these patients. Seve nteen 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 patie nt lymphocytes expressed most Valpha and Vbeta sub-family specificitie s, similarly to the lymphocytes of healthy donors (n = 10). This sugge sts that immunodepression in advanced cancer patients is not related t o major deletions in their T-cell repertoires. We also compared the me an relative expression of each V-sub-family specificity of patients an d healthy donors by quantitative densitometric analysis. We found sign ificant differences in 4 Vbeta specificities (and no Valpha). Our anal ysis identified unique T-cell sub-sets putatively involved in the mech anisms leading to immunodepression in advanced cancer patients. Altern atively, the observed differences in terms of Vbeta specificity expres sion may reflect the host response against the tumor.