EVIDENCE FOR T-CELL CLONAL EXPANSION IN A PATIENT WITH SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Squamous cell carcinomas of the head and neck (SCCHN) often contain a large mononuclear cell infiltrate, composed mainly of T-Lymphocytes wh ich could reflect an in situ immune reaction against the malignant SCC HN cells. We analyzed the molecular structure of the T-celI receptor ( TCR) alpha and beta chains expressed by lymphocytes in the tumor, peri pheral blood (PBMC), and in the peritumoral tissue in six cases of loc alized SCCHN. We first determined V alpha and V beta gene segment subf amily usage by polymerase chain reaction using a panel of V subfamily- specific oligonucleotide primers (V alpha 1-w29 and V beta 1-w24). An apparently unrestricted usage of V alpha or V beta gene segment snbfam ilies was observed for all three samples from the six cases examined. No major difference was observed in T-celI receptor repertoire express ion of PBMC between SCCHN and healthy donors, making unlikely the expr ession of putative tumor-related superantigen(s) in these patients. In tersample comparisons for a given V alpha or V beta T-cell receptor sp ecificity revealed some differences in V gene segment usage in tumor-i nfiltrating lymphocytes versus PBMC. A detailed analysis of these V se gment subfamily specificities (cloning followed by sequencing and CDW size distribution analysis) in one patient revealed the presence of re current T-cell receptor transcripts tie., identical V-N-J sequences) i n the tumor (e.g., 40%) and in PBMC (e.g., 75%). These results show th at unique T-cell subpopulations are clonally amplified in SCCHN patien ts, possibly as a consequence of antigen-driven selection.