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Late-breaking abstracts
Immune cell types
839 Transcriptomic profiling of T-cell populations in non-muscle invasive and muscle invasive bladder cancer
  1. Viktor Sincic1,
  2. Milad Abolhalaj1,
  3. Henrik Lilljebjörn1,
  4. Alar Aab1,
  5. Karin Hagerbrand2,
  6. Peter Ellmark3,
  7. Thoas Fioretos1,
  8. Carl Borrebaeck1,
  9. Fredrik Liedberg4 and
  10. Kristina Lundberg1
  1. 1Lund University, LUND, Sweden
  2. 2Alligator Bioscience AB, Lund, Sweden
  3. 3Alligator Bioscience AB. Lund University, Lund, Sweden
  4. 4Skåne University Hospital, Lund University, Lund, Sweden

Abstract

Background Bladder cancer is categorized as non-muscle invasive (NMIBC) or muscle invasive (MIBC). NIMBC makes up around 70% of the cases and although it is less aggressive, the recurrence rate is 50-70%, thus requiring extensive monitoring. Additionally, there is a risk of progression into MIBC with a 5-year survival of only 50% even when treated with radical cystectomy. Immune checkpoint inhibitors have shown promising results for treatment of bladder cancer; however, only around 30% of patients have a therapeutic effect and novel therapies are thus required. With the aim of pinpointing novel targets for T-cell based therapy, we have performed transcriptomic profiling of specific T cell populations in MIBC and NMIBC, as well as in control bladder tissue.

Methods Muscle-invasive (n=7) as well as non-muscle invasive (n=13) bladder tumor biopsies were obtained from untreated patients and control bladder tissue (n=7). Upon digestion, cells were stained with an antibody panel to enable sorting of CD8+ cytotoxic T-cells (CD8T), CD4+ T-helper cells (Th) and regulatory T-cells (Treg) using fluorescence activated cell sorting. RNA was extracted and subject to sequencing. Differential gene expression analysis was performed, using DESeq2 (genes with padj

Results Principal component analysis demonstrated that CD8T, unlike Th and Tregs, cluster according to the invasiveness of the disease. Accordingly, many genes were significantly differentially expressed between CD8T in MIBC and NMIBC compared to control, and also between CD8T in MIBC compared to NMIBC. Several genes associated with CD8 T-cell exhaustion were significantly upregulated in MIBC compared to both NMIBC and control. Further, GSEA results indicated biological differences of the CD8T compartment between different tumor stages.

Conclusions The gene expression profiles of CD8 T-cells were significantly different in NMIBC, MIBC and control. The transcriptional profiles give clues on biological differences and disease progression and can be relevant for development of novel treatment strategies.

Ethics Approval The study was approved by the Regional Ethics Committee (EPN - Regionala Etikprövningsnämnden i Lund), approval number 2017/34.

Consent Written informed consent was obtained from all patients included in the study.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/jitc-2020-SITC2020.0839

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