Oesophageal cancer immunophenotyping - CRUK Accelerator
Research type
Research Study
Full title
Immunophenotyping in oesophageal cancer is predictive of overall survival.
IRAS ID
240817
Contact name
Manuel Salto-Tellez
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
1 years, 5 months, 26 days
Research summary
Oesophageal(OES) is a heterogeneous malignancy, for which treatment has principally been radical surgical resection and cytotoxic chemotherapy. Our aim is to assess the immune-biomarker landscape in the largest study of its kind, demonstrating the therapeutic potential of immunotherapy in OES. The Northern Ireland Biobank approved project NIB15-0168 has interrogated 166 pre-therapeutic OES surgical resections in primary oesophageal adenocarcinomas in tissue microarray (TMA) format for a range of immune, immune checkpoint, oncogenic proteins and mis-match repair biomarkers. To date, biomarkers CD3, CD4, CD8, CD45R0, ICOS, IDO, PD-1, PD-L1, HER2, P53, MLH1, MSH2, MSH6 and PMS2 have been assessed within our OES cohort and related to overall survival (OS). Interestingly we have novel correlations of these biomarkers to be important in patient OS duration with many of these biomarkers.
We have validated the expression of these biomarkers via digital pathological analysis. We have also extensively validated our immunohistochemistry technique for its sensitivity and specificity of these biomarkers, following strict AQ/QC processes to determine the in situ expression across our cohort.
We feel that it is now essential to confirm the presence of these immune and immune checkpoint proteins in an additional cohort of cases. In addition to the biomarkers assessed, our goal is to profile addition key proteins for their role in the tumour-immune milieu. This would enable confirmation that these biomarkers are involved in patient OS and may provide novel diagnostic subgroups which could be good candidates for immune therapy in OES. This would be a significant breakthrough for cancer immunology.Lay summary of study results:
Esophageal adenocarcinoma is a type of cancer of the gullet with bad prognosis, usually because it is diagnosed late and at an advanced stage.
In this study we tested samples of patients who had been diagnosed wit this cancer type. We looked for clues in the reaction that the patient's own immune systems create against the cancer, and the immune responses of the cancer itself.
In this work we identified that a general marker of immune response (CD45RO+) and a marker sometimes upregulated int he tumour (ICOS+), when together, showed a better prognosis.
This study, indirectly, was proof that targeting the immune system could be favorable to treat this cancer subtype.REC name
London - South East Research Ethics Committee
REC reference
18/LO/0161
Date of REC Opinion
26 Jan 2018
REC opinion
Favourable Opinion