Evidence for T-cell clonal expansion in a patient with squamous cell carcinoma of the head and neck.

Abstract

Squamous cell carcinomas of the head and neck (SCCHN) often contain a large mononuclear cell infiltrate, composed mainly of T-lymphocytes which could reflect an in situ immune reaction against the malignant SCCHN cells. We analyzed the molecular structure of the T-cell receptor (TCR) alpha and beta chains expressed by lymphocytes in the tumor, peripheral blood (PBMC), and in the peritumoral tissue in six cases of localized SCCHN. We first determined V alpha and V beta gene segment subfamily 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 subfamilies was observed for all three samples from the six cases examined. No major difference was observed in T-cell receptor repertoire expression of PBMC between SCCHN and healthy donors, making unlikely the expression of putative tumor-related superantigen(s) in these patients. Intersample comparisons for a given V alpha or V beta T-cell receptor specificity revealed some differences in V gene segment usage in tumor-infiltrating lymphocytes versus PBMC. A detailed analysis of these V segment subfamily specificities (cloning followed by sequencing and CDR3 size distribution analysis) in one patient revealed the presence of recurrent T-cell receptor transcripts (i.e., identical V-N-J sequences) in the tumor (e.g., 40%) and in PBMC (e.g., 75%). These results show that unique T-cell subpopulations are clonally amplified in SCCHN patients, possibly as a consequence of antigen-driven selection.