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Urol Oncol. 2019 May 15. pii: S1078-1439(19)30144-9. doi: 10.1016/j.urolonc.2019.04.011. [Epub ahead of print]

Human urothelial bladder cancer generates a clonal immune response: The results of T-cell receptor sequencing.

Author information

1
Department of Urology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY. Electronic address: asankin@montefiore.org.
2
Department of Urology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY; Department of Microbiology and Immunology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY.
3
Department of Urology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY.

Abstract

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.

KEYWORDS:

Immunotherapy; T-cell receptor; Urinary bladder neoplasm

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