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

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  1. Risk of cardiovascular events in men treated for prostate cancer compared with prostate cancer-free men

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  2. Statin use and risk of contralateral breast cancer: a nationwide cohort study

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  3. Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma

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  1. Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts

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  2. The real-world impact of modern treatments on the survival of patients with metastatic melanoma

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  3. High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals

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  4. Acquired resistance to cancer immunotherapy

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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.

Original languageEnglish
JournalBritish Journal of Cancer
Volume120
Issue number4
Pages (from-to)424-434
Number of pages11
ISSN0007-0920
DOIs
Publication statusPublished - 19 Feb 2019

ID: 56748805