Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session

177P - Ubiquitous neoantigens as targets for T cell recognition in a patient with metastatic pancreatic neuroendocrine tumour

Date

12 Dec 2024

Session

Poster Display session

Presenters

Jean-Benoit Tanis

Citation

Annals of Oncology (2024) 24 (suppl_1): 1-20. 10.1016/iotech/iotech100741

Authors

J. Tanis1, K. McCann2, E. Castaneda3, J. Thomas2, A. Bailey2, J. Pickering2, P. Singh1, A. Tiwari1, E. Currall1, L. Chudley1, J. Cave4, A. Takhar5, S.P. Schoenberger3, J. Greenbaum3, N. Savelyeva1, P. Vijayanand3, G. Seumois3, C.H.H. Ottensmeier1

Author affiliations

  • 1 University of Liverpool, Liverpool/GB
  • 2 University of Southampton - Cancer Research UK Centre, Southampton/GB
  • 3 La Jolla Institute for Immunology, La Jolla/US
  • 4 Southampton General Hospital - University Hospital Southampton NHS Trust, Southampton/GB
  • 5 Southampton General Hospital, Southampton/GB

Resources

This content is available to ESMO members and event participants.

Abstract 177P

Background

Mutation-derived neoantigens, usually identified from the primary cancer, are being targeted by vaccination in clinical trials. However, clinical success in patients with extensive metastatic disease is limited, possibly due to poor neoantigen selection. Targeting ubiquitous neoantigens - present in all metastatic sites - is appealing. We investigated the presence of ubiquitous neoantigens and their T-cell recognition in a patient with treatment-naïve metastatic pancreatic neuroendocrine tumour (PNET), analysing the primary tumour and 13 synchronous nodal metastases.

Methods

Bulk RNA sequencing, whole exome sequencing and mutation calling were performed on all samples; β-chain T-cell receptor (TCR) sequencing was performed on eight metastatic sites. Mutation-associated long peptides (MUT_LPs) and predicted minimal neoepitopes (MUT_ME) were synthesized. IFN-γ ELISpot and single-cell RNA/TCR sequencing (scRNA/TCRseq) were undertaken on MUT_LPs/MEs stimulated peripheral blood mononuclear cells (PBMCs) after in vitro expansion. ScTCRseq was performed on MUT_ME-MHC class I tetramer-positive CD8 T-cells. TCR overlap was evaluated between metastatic sites, MUT_LP/ME expanded and tetramer-positive T-cells.

Results

We identified a median of 88 non-synonymous mutations (range 64-204) per site, indicating low tumour-mutation burden (TMB). Seven mutations were identified in all metastatic sites. T cell recognition was shown by ELISpot for two MUT_LPs and one MUT_ME (MUT_NPTX2). scRNAseq of MUT_NPTX2_ME/LP-expanded PBMCs showed activated CD8 T-cells; 94.8% of these cells had TCRs matching MUT_NPTX2_ME-MHC class I tetramer-positive clones. Putative MUT_NPTX2-reactive CD8 T-cells were found in all analysed metastatic sites (1.9%-7.0% of reads per site), with evidence of expansion.

Conclusions

In a low TMB setting, we found seven ubiquitous mutations. One neoantigen showed T-cell recognition, with reactive T-cells present in all analysed metastatic sites. This novel finding suggests that ubiquitous neoantigens-targeting vaccines, possibly combined with immune-checkpoint inhibitors, could be promising for patients with extensive metastatic PNET.

Legal entity responsible for the study

Prof. Christian Ottensmeier.

Funding

Whittaker Fund.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.