Clonality of tumor-infiltrating lymphocytes in human urinary bladder carcinoma.
The immune system has been implicated in the control of bladder tumor growth. To evaluate the clonality of bladder tumor-infiltrating T lymphocytes (TILs) in vivo, we studied the T-cell antigen receptor (TCR) repertoire in tumor biopsy specimens from 10 patients with transitional-cell carcinoma (TCC) of the bladder. Nine patients had a primary tumor, and one had a multifocal disease, consisting of two bladder tumors and three bilateral upper urinary tract sites of involvement. The following specimens from the nine patients with a primary tumor also were analyzed: a recurrent tumor from four patients, a metastatic lymph node from one patient, and peripheral blood from five patients. We used a high-resolution polymerase chain reaction (PCR) method to determine CDR3 (complementarity-determining region 3) size lengths of TCR beta-chain transcripts. Oligoclonal T-cell expansion was identified in all specimens, with a larger number of expanded clones in the tumors than in peripheral blood. Expanded clones were identified in several beta-chain variable region (BV) subfamilies and varied from one patient to the next and also in different specimens from the same patient. However, a number of clones with the same VJ combination and the same CDR3 size were identified in a given patient (in specimens collected either simultaneously or at different times), suggesting homogeneity in the immunogenic environment. Clonal T-cell expansion in patients with bladder cancer may reflect prolonged exposure of T lymphocytes to tumor antigens. Our findings provide a basis for functional studies to elucidate T lymphocyte-bladder tumor cell interactions.
Velotti
F
F
Groupe d'Etude des Tumeurs Urologiques (GETU), Formation associée Claude Bernard, Université Paris XII, Hôpital Henri Mondor, Créteil, France.
Chopin
D
D
Gil-Diez
S
S
Maille
P
P
Abbou
C C
CC
Kourilsky
P
P
Even
J
J
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology
D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta