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 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.
Caignard
A
A
INSERM U333, Institut Gustave Roussy, Villejuif, France.
Dietrich
P Y
PY
Morand
V
V
Lim
A
A
Pannetier
C
C
Leridant
A M
AM
Hercend
T
T
Even
J
J
Kourilsky
P
P
Triebel
F
F
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics
D017931:DNA Primers; D004273:DNA, Neoplasm; D016693:Receptors, Antigen, T-Cell, alpha-beta