Human urothelial bladder cancer generates a clonal immune response: The results of T-cell receptor sequencing.
Aged
Carcinoma, Transitional Cell
/ immunology
Clonal Selection, Antigen-Mediated
Female
Humans
Lymphocytes, Tumor-Infiltrating
/ metabolism
Male
Prospective Studies
Receptors, Antigen, T-Cell
/ genetics
T-Lymphocyte Subsets
/ metabolism
Tumor Microenvironment
/ immunology
Urinary Bladder Neoplasms
/ immunology
Immunotherapy
T-cell receptor
Urinary bladder neoplasm
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
01
03
2019
revised:
22
03
2019
accepted:
12
04
2019
pubmed:
20
5
2019
medline:
20
8
2020
entrez:
20
5
2019
Statut:
ppublish
Résumé
High T-cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer. To determine if TCR repertoire is more clonal in tumors than in benign inflammation. We prospectively identified 12 patients with bladder lesions undergoing transurethral resection. Specimens were collected at time of transurethral resection and stored at -80C. DNA was extracted and high throughput DNA sequencing of the CDR3 region of the TCR beta chain using the immunoSEQ assay (Adaptive Biotechnologies) was performed. T-cell fraction, clonal dominance, and maximum frequency of TCR clone were assessed. Of the 12 bladder lesions resected, 3 of 12 were cT0, 3 of 12 were cTa, 3 of 12 were cT1, and 3 of 12 were cT2 or greater. The median number of T cells in urothelial carcinoma specimens (UC+) and benign (UC-) specimens was 5,569 and 25,872, respectively. The number of unique TCRs sequenced in UC+ and UC- specimens was 3,069 and 9,680, respectively. The median tumor infiltrating lymphocyte percentage in UC+ and UC- specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as evidenced by identification of a specific T-cell clone being present in up to 17% of the total tumor infiltrating lymphocyte pool, in contrast to 2% among UC- specimens. Primary urothelial tumors contain clonally expanded T-cell populations. These data support the hypothesis that bladder tumors induce an antigen-driven immunogenic host response, in contrast to the benign inflammatory response, which does not appear to demonstrate any T-cell clonal dominance.
Sections du résumé
BACKGROUND
High T-cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer.
OBJECTIVE
To determine if TCR repertoire is more clonal in tumors than in benign inflammation.
METHODS
We prospectively identified 12 patients with bladder lesions undergoing transurethral resection. Specimens were collected at time of transurethral resection and stored at -80C. DNA was extracted and high throughput DNA sequencing of the CDR3 region of the TCR beta chain using the immunoSEQ assay (Adaptive Biotechnologies) was performed. T-cell fraction, clonal dominance, and maximum frequency of TCR clone were assessed.
RESULTS
Of the 12 bladder lesions resected, 3 of 12 were cT0, 3 of 12 were cTa, 3 of 12 were cT1, and 3 of 12 were cT2 or greater. The median number of T cells in urothelial carcinoma specimens (UC+) and benign (UC-) specimens was 5,569 and 25,872, respectively. The number of unique TCRs sequenced in UC+ and UC- specimens was 3,069 and 9,680, respectively. The median tumor infiltrating lymphocyte percentage in UC+ and UC- specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as evidenced by identification of a specific T-cell clone being present in up to 17% of the total tumor infiltrating lymphocyte pool, in contrast to 2% among UC- specimens.
CONCLUSIONS
Primary urothelial tumors contain clonally expanded T-cell populations. These data support the hypothesis that bladder tumors induce an antigen-driven immunogenic host response, in contrast to the benign inflammatory response, which does not appear to demonstrate any T-cell clonal dominance.
Identifiants
pubmed: 31103336
pii: S1078-1439(19)30144-9
doi: 10.1016/j.urolonc.2019.04.011
pii:
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
810.e1-810.e5Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.