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Lunch & Poster Display session

30P - Transcriptomic landscape of tumour cells undergoing T-cell attack

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Aishwarya Gokuldass

Citation

Annals of Oncology (2019) 30 (suppl_11): xi1-xi11. 10.1093/annonc/mdz447

Authors

A. Gokuldass1, A. Schina1, M. Lauss2, K. Harbst2, C.A. Chamberlain3, A. Draghi4, M.C.W. Westergaard3, M. Nielsen3, K. Papp5, Z.M. Sztupinski6, I. Casabi7, I.M. Svane8, Z. Szallasi6, G.B. Jönsson2, M. Donia9

Author affiliations

  • 1 National Center For Cancer Immune Therapy, Department Of Hematology, Herlev Hospital, 2730 - Herlev/DK
  • 2 Oncology And Pathology, Lund University, Lund/SE
  • 3 Department Of Oncology, Herlev Hospital - National Center for Cancer Immune Therapy (CCIT-DK), 2730 - Herlev/DK
  • 4 Ccit-center For Cancer Immune Therapy, Herlev Hospital - National Center for Cancer Immune Therapy, 2730 - Herlev/DK
  • 5 Physics Of Complex Systems, Eotovos lorand University, Budapest/HU
  • 6 Translational Cancer Genomics, Danish Cancer Soceity, Copenhagen/DK
  • 7 Physics, ELTE Eötvös Loránd University, Budapest/HU
  • 8 Nationalt Center For Cancer Immunterapi, Ccit-dk, Herlev Hospital, 2730 - Herlev/DK
  • 9 Oncology, Herlev Hospital, 2730 - Herlev/DK
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Resources

Abstract 30P

Background

The study of crosstalks between cancer cells and T cells in the tumour microenvironment (TME) can inform on tumour immune escape and help in predicting responses to immunotherapy. By reproducing in vitro how tumour infiltrating lymphocytes (TILs) interact with cancer cells, novel methodologies may allow a thorough characterization of the transcriptomic changes induced in tumours undergoing a T cell attack (TuTACK).

Methods

Thirteen pairs of highly tumour-reactive TILs and autologous cancer cell lines, covering four distinct tumour types, were selected and co-cultured to induce a cytostatic effect in tumour cultures. The global TuTACK transcriptome was characterized, and a TuTACK gene signature was extracted to be tested for prediction of response to anti-PD-1/anti-PD-L1.

Results

We showed that an autologous T cell attack induced large transcriptomic changes in tumours, that were independent of IFN-g signaling. Transcriptomic changes were tumour-type independent and allowed the identification of a gene-set (TuTACK gene-set) containing 256 genes covering 55 defined biological processes, that included several potential actionable adaptive immune resistance pathways. We extracted a 14-gene signature (TuTACK signature) that allowed a novel scoring of the TME. The TuTACK score correlated well to the estimated immunological activity in the TME (measured by the T cell-inflamed gene expression profile or GEP), and was predictive of response to anti-PD-1/PD-L1 therapy across 26 tumour types (Spearman R = 0.54, Pearson R = 0.57) outperforming the T cell-inflamed GEP score (Spearman R = 0.25, Pearson R = 0.34) and with a comparable predictive power to the tumour mutational burden (TMB; Spearman R = 0.65, Pearson R = 0.56). The TuTACK score was only moderately correlated to the TMB (Spearman R = 0.36; Pearson R = 0.53), indicating that these biomarkers may be independent.

Conclusion

TuTACK measured the effects of an immune response rather than its activity and it represents an innovative method to identify immunologically hot tumours. Our findings suggested that TuTACK may allow better patient selection in immunotherapy clinical trials and provide hints to improve the treatment of “hot” tumours resistant to current immunotherapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Danish Cancer Society (grant number R148-A9862); The Lundbeck Foundation (grant number R233-2016-3728); The Capital Region of Denmark Research Foundation (grant number R146-A5693); The National Research, Development and Innovation Fund of Hungary (FIEK_16-1-2016-0005).

Disclosure

All authors have declared no conflicts of interest.

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