Immune response gene expression analysis and response to radical chemoradiation in bladder cancer
Anjanappa, Milan Roberts, D. Reeves, K. Song, Yee Pei Akturk, N Choudhury, Ananya
Anjanappa, Milan
Roberts, D.
Reeves, K.
Song, Yee Pei
Akturk, N
Choudhury, Ananya
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Abstract
Purpose or Objective
The presence of tumour infiltrating lymphocytes (TILs) is
prognostic in a number of solid tumours such as colon, lung
and breast. An immune supressed tumour
microenvironment is a poor prognostic factor thought to
be due to a limited host response to cancer cell death. The
immune response gene analysis enables characterisation of
the TILs and the responsible pathways. Bladder cancer is
known to be influenced by immune modulation. We
hypothesised that the immune genotype of muscleinvasive
bladder cancers treated with radical
chemoradiotherapy would stratify for distant failure.
Material and Methods
Between 2012 and 2014, fifty patients with muscle invasive
bladder cancer underwent radical radiotherapy (52.5Gy in
20 fractions) with concurrent gemcitabine (100mg/m2) as per institutional protocol (NCT01343121). Forty-eight
tumour tissue sample blocks were available for
analysis. Next generation sequencing of transcriptomic
RNA was performed evaluating the expression of 395
immune response genes. Gene expression was categorised
relative to validated house-keeping genes and analysed
with respect to patients who had relapsed with distant
metastases.
Results
After 3 years of follow up, 6 patients had developed distant
metastases. In these patients, CD3 and IL10 expression was
reduced indicating a low T-cell and monocyte infiltrate. MTOR,
PIK3CA and PTPN11 were elevated suggesting
activation of signalling pathways often found in aggressive
cancers.
Conclusion
This study is hypothesis generating, but provides data
supporting a relationship between the immune tumour
microenvironment and poor response to treatment and
development of distant metastases. With the PIK3CAMTOR-
AKT and RAS-MAPK pathways implicated with an
increased aggressive phenotype and resistance to anti-
PD1/PDL1 therapy, immune response gene signatures
should be investigated as both prognostic and predictive
biomarkers in bladder cancer.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Parry M, Cowling T, Sujenthiran A, Nossiter J, Berry B, Cathcart P, et al. PO-1178: Identifying skeletal-related events for prostate cancer in routinely collected hospital data. Radiotherapy and Oncology . 2020 Nov;152:S620.