Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

PD-1+ polyfunctional T cells dominate the periphery after tumour-infiltrating lymphocyte therapy for cancer

Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Wulff Westergaard, Marie Christine, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Szomolay, Barbara, Ott, Sascha, Dolton, Garry, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew and Svane, Inge Marie 2017. PD-1+ polyfunctional T cells dominate the periphery after tumour-infiltrating lymphocyte therapy for cancer. Clinical Cancer Research 23 (19) , pp. 5779-5788. 10.1158/1078-0432.CCR-16-1692

[img]
Preview
PDF - Accepted Post-Print Version
Download (2MB) | Preview

Abstract

Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TILs) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs one month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here we studied the dynamics of bulk tumor-reactive CD8+ T cell populations in patients with metastatic melanoma following treatment with TILs. Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of sixteen patients treated with TILs Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD- 1 and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year post-infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor-antigens had similar differentiation status. Conclusions: We demonstrated that tumor-reactive CD8+ T cell subsets which persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype and express high levels of PD-1. These partially differentiated PD-1+ polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2-mediated inhibition.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Association for Cancer Research
ISSN: 1078-0432
Funders: Wellcome Trust
Date of First Compliant Deposit: 19 July 2017
Date of Acceptance: 26 June 2017
Last Modified: 11 Jul 2018 19:06
URI: http://orca-mwe.cf.ac.uk/id/eprint/102640

Citation Data

Cited 8 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics