Ex vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells.
AffiliationGynaecological Oncology, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
MetadataShow full item record
AbstractEpithelial ovarian cancer (EOC) is the leading cause of gynaecological cancer-related death in Europe. Although most patients achieve an initial complete response with first-line treatment, recurrence occurs in more than 80% of cases. Thus, there is a clear unmet need for novel second-line treatments. EOC is frequently infiltrated with T lymphocytes, the presence of which has been shown to be associated with improved clinical outcomes. Adoptive T-cell therapy (ACT) using ex vivo-expanded tumour-infiltrating lymphocytes (TILs) has shown remarkable efficacy in other immunogenic tumours, and may represent a promising therapeutic strategy for EOC. In this preclinical study, we investigated the efficacy of using anti-CD3/anti-CD28 magnetic beads and IL-2 to expand TILs from freshly resected ovarian tumours. TILs were expanded for up to 3 weeks, and then subjected to a rapid-expansion protocol (REP) using irradiated feeder cells. Tumours were collected from 45 patients with EOC and TILs were successfully expanded from 89.7% of biopsies. Expanded CD4+ and CD8+ subsets demonstrated features associated with memory phenotypes, and had significantly higher expression of key activation and functional markers than unexpanded TILs. Expanded TILs produced anti-tumour cytokines when co-cultured with autologous tumour cells, inferring tumour cytotoxicity. Our findings demonstrate that it is possible to re-activate and expand tumour-reactive T cells from ovarian tumours. This presents a promising immunotherapy that could be used sequentially or in combination with current therapeutic strategies.
CitationEx vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells. 2018, Cancer Immunol Immunother
JournalCancer Immunology, Immunotherapy
- Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer.
- Authors: Webb JR, Milne K, Watson P, Deleeuw RJ, Nelson BH
- Issue date: 2014 Jan 15
- Expansion of Tumor-reactive T Cells From Patients With Pancreatic Cancer.
- Authors: Meng Q, Liu Z, Rangelova E, Poiret T, Ambati A, Rane L, Xie S, Verbeke C, Dodoo E, Del Chiaro M, Löhr M, Segersvärd R, Maeurer MJ
- Issue date: 2016 Feb-Mar
- In search of specific cytotoxic T lymphocytes infiltrating or accompanying human ovarian carcinoma.
- Authors: Apiranthitou-Drogari M, Paganin C, Bernasconi S, Losa G, Maneo A, Colombo N, Mantovani A, Allavena P
- Issue date: 1992
- Differential expression of cytokine transcripts in human epithelial ovarian carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour, tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour cell lines.
- Authors: Nash MA, Lenzi R, Edwards CL, Kavanagh JJ, Kudelka AP, Verschraegen CF, Platsoucas CD, Freedman RS
- Issue date: 1998 May
- Phenotypic and functional characterisation of tumour-infiltrating lymphocytes derived from thyroid tumours.
- Authors: Lee RS, Schlumberger M, Caillou B, Pages F, Fridman WH, Tartour E
- Issue date: 1996 Jun