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Poster display session

3748 - Urine-derived lymphocytes (UDLs) as a non-invasive surrogate marker of tumour infiltrating lymphocytes (TILs) in patients with muscle invasive bladder cancer (MIBC)

Date

10 Sep 2017

Session

Poster display session

Presenters

Yien Ning Sophia Wong

Citation

Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Authors

Y.N.S. Wong1, K. Joshi1, P. Khetrapal2, M. Ismail3, J. Linares4, A.U. Akarca4, J.L. Reading1, A. Furness1, A. Feber2, U. McGovern5, C. Swanton6, A. Freeman7, T.P. Briggs2, J. Kelly2, T. Marafioti4, K.S. Peggs1, T. Powles8, B.M. Chain3, M. Linch1, S.A. Quezada1

Author affiliations

  • 1 Ucl Cancer Institute, UCL - University College London, WC1E 6DD - London/GB
  • 2 Department Of Urology, UCL - University College London, London/GB
  • 3 Division Of Infection And Immunity, UCL - University College London, London/GB
  • 4 Department Of Cellular Pathology, UCL - University College London, London/GB
  • 5 Medical Oncology, University College London Hospital, London/GB
  • 6 Translational Cancer Therapeutics, The Francis Crick Institute, NW1 1AT - London/GB
  • 7 Department Of Histopathology, University College London Hospital, London/GB
  • 8 Centre For Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ - London/GB
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Resources

Abstract 3748

Background

The therapeutic targeting of PD-1 and PD-L1 has led to durable responses in metastatic bladder cancer, yet the majority of patients (pts) fail to respond. Here, we characterised the immune phenotype and TCR repertoire in tumour and UDLs in patients with MIBC for the identification of potential T cell biomarkers of response and resistance to checkpoint blockade.

Methods

Matched bladder tumour, normal urothelium (NU), urine and peripheral blood mononuclear cells (PBMC) were collected from 30 pts undergoing cystectomy. Multi-parametric flow cytometry and immunohistochemistry were used to determine the abundance of CD8+, CD4+FoxP3-(CD4eff) and CD4+FoxP3+(Treg) T cell subsets and co-inhibitory (PD-1, CTLA-4, TIM-3) and co-stimulatory (ICOS, 4-1BB) immune checkpoint molecules. T cell receptor (TCR) repertoire was determined using quantitative high throughput sequencing of α and β TCR chains followed by Decombinator bioinformatics analysis.

Results

UDLs were identified in 19/24 (80%) of MIBC pts with tumour in situ compared to 3/6 (50%) pts with pathological downstaging (pT0) following neo-adjuvant therapy. Urine, tumour and PBMC specimens were found to have a similar CD8/Treg ratio that was significantly higher in NU. Co-stimulatory and co-inhibitory checkpoint molecules were similarly distributed across CD8+, CD4eff and Treg within tumour, urine and NU compartments, however significantly different to PBMC, irrespective of prior treatment. Preliminary analysis revealed a higher degree of similarity between the TCR repertoires of urine and matched tumour as compared with urine and NU or urine and PBMC samples.

Conclusions

These data suggest that UDLs are an accessible source of T cells from pts with MIBC that accurately map the immune landscape of TILs. UDL analysis represents a liquid biopsy to inform clinically relevant immunological parameters, including the CD8/Treg ratio, target checkpoint expression and TCR repertoire, irrespective of prior treatment. Further translational studies are ongoing to evaluate whether UDL analysis may serve as a non-invasive, dynamic biomarker to predict immunotherapy outcome in MIBC.

Clinical trial identification

University College London (UCL)/University College London Hospital (UCLH) BioBank for Health and Human Disease (NC06.11)

Legal entity responsible for the study

UCL/UCLH

Funding

UCL/UCLH

Disclosure

C. Swanton: Grants/research supports: Pfizer Honoraria or consultation fees: Roche Ventana, Celgene, Pfizer, Novartis; Stock shareholder: Grail, Epic Biosciences, Apogen Biotechnologies, Achilles Therapeutics. T. Powles: Research funding: AstraZeneca and Roche; Honoraria AstraZeneca, Roche, Merck, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

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