Translational Therapeutics

Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

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  • A Correction to this article was published on 19 March 2019

Abstract

Background

Solid malignancies are frequently infiltrated with T cells. The success of adoptive cell transfer (ACT) with expanded tumour-infiltrating lymphocytes (TILs) in melanoma warrants its testing in other cancer types. In this preclinical study, we investigated whether clinical-grade TILs could be manufactured from ovarian cancer (OC) tumour specimens.

Methods

Thirty-four tumour specimens were obtained from 33 individual patients with OC. TILs were analysed for phenotype, antigen specificity and functionality.

Results

Minimally expanded TILs (Young TILs) were successfully established from all patients. Young TILs contained a high frequency of CD3+ cells with a variable CD4/CD8 ratio. TILs could be expanded to clinical numbers. Importantly, recognition of autologous tumour cells was demonstrated in TILs in >50% of the patients. We confirmed with mass spectrometry the presentation of multiple tumour antigens, including peptides derived from the cancer-testis antigen GAGE, which could be recognised by antigen-specific TILs. Antigen-specific TILs could be isolated and further expanded in vitro.

Conclusion

These findings support the hypothesis that patients with OC can benefit from ACT with TILs and led to the initiation of a pilot clinical trial at our institution .

Trial Registration

clinicaltrials.gov: NCT02482090.

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Data availability

Data and material generated and analysed during the current study can be available upon reasonable request to the corresponding author.

Change history

  • 19 March 2019

    Since the publication of this paper, the authors noticed that the funding information was not complete. The correct funding information is now shown in the Acknowledgements section.

    Acknowledgements

    The studies were supported by grants from the OvaCure Foundation, the Danish Cancer Society Research Foundation, the Anticancer Fund, Aase og Ejnar Danielsens Foundation and the Independent Research Fund Denmark (grant number DFF-4183-00597).

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Acknowledgements

Lissen Ingvartsen is acknowledged for assistance in patient inclusion. The studies were supported by grants from the OvaCure Foundation, the Danish Cancer Society Research Foundation, the Anticancer Fund and Aase og Ejnar Danielsens Foundation.

Authors’ contributions

M.C.W.W. conceived and designed experiments, developed methodology, acquired data, analysed and interpreted data, and wrote the manuscript. C.C. acquired data, analysed and interpreted data, and wrote the manuscript. R.A., J.W.K., M.P. and C.F. acquired data and proof-read the manuscript. T.H. and H.L. acquired data, analysed and interpreted data, and wrote the manuscript. G.C., M.B.-S., M.D. and I.M.S. supervised the study.

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Correspondence to Inge Marie Svane.

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Competing interests

The authors declare no competing interests.

Ethics approval

The Danish National Committee on Health Research Ethics approved the scientific use of the patient material (protocol number H-2-2014-055).

Consent for publication

All patients included in the study have signed informed consent to participate.

Note

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

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A correction to this article is available online at https://doi.org/10.1038/s41416-019-0425-6.

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Westergaard, M.C.W., Andersen, R., Chong, C. et al. Tumour-reactive T cell subsets in the microenvironment of ovarian cancer. Br J Cancer 120, 424–434 (2019) doi:10.1038/s41416-019-0384-y

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