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196423_1_merged_1528449684 samer BCG paper.pdf (1.43 MB)

Baseline cytokine profiles of tuberculin-specific CD4 T-cells in non-muscle invasive bladder cancer may predict outcomes of BCG immunotherapy within reach?

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posted on 2023-06-09, 14:47 authored by Samer Jallad, Philip Thoma, Melanie NewportMelanie Newport, Florian KernFlorian Kern
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy preserves the bladder after resection of high-risk non-muscle invasive bladder cancer (NMIBC). About 30% of patients experience treatment failure, which cannot be predicted a priori and carries a high risk of disease progression. We examined the in vitro tuberculin-responsiveness of CD4+ T cells before BCG immunotherapy in 42 patients with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing CD4+ T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation. Tuberculin-induced secreted mediators were measured by electrochemiluminescence. We correlated the results with recurrence-free patient survival 6 months after induction. A tuberculin-induced, secreted, IL2 concentration > 250 pg/ml was the best predictor of recurrence-free survival, providing 79% sensitivity, 86% specificity (AUC = 0.852, P = 0.000), and overall correct classification in 78.6% of cases. In 50% of patients later experiencing recurrence, but not in any of the recurrence-free survivors, IL2 secretion was < 120 pg/ml. Other parameters predicting recurrence-free survival included secreted IFN? (AUC = 0.796, P = 0.002) and the frequencies of TNF-producing (TNF+) CD4+ T cells (AUC = 0.745, P = 0.010). 'Polyfunctional' CD4+ T cells (IFN?+/IL2+/ TNF+) were significantly associated with recurrence-free survival (AUC = 0.801, P = 0.002). Thus, the amount of IL2 secretion from CD4+ T cells after overnight in vitro incubation with tuberculin predicted the outcome of BCG immunotherapy. As many as half of potential BCG failures could be identified before induction therapy is begun, enabling better choices regarding treatment.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Cancer Immunology Research

ISSN

2326-6066

Publisher

American Association for Cancer Research

Issue

10

Volume

6

Page range

1212-1219

Department affiliated with

  • Clinical and Experimental Medicine Publications

Research groups affiliated with

  • Centre for Global Health Policy Publications
  • Wellcome Trust Brighton and Sussex Centre for Global Health Research Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-08-28

First Open Access (FOA) Date

2019-08-17

First Compliant Deposit (FCD) Date

2018-08-24

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