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PD-1 + polyfunctional T cells dominate the periphery after tumor-infiltrating lymphocyte therapy for cancer
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Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Westergaard, Marie Christine Wulff, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Szomolay, Barbara, Ott, Sascha, Dolton, Garry, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew K. and Svane, Inge Marie (2017) PD-1 + polyfunctional T cells dominate the periphery after tumor-infiltrating lymphocyte therapy for cancer. Clinical Cancer Research, 23 (19). pp. 5779-5788. doi:10.1158/1078-0432.CCR-16-1692 ISSN 1078-0432.
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WRAP-PD-1-polyfunctional-T-cells-dominate-periphery-Ott-2017.pdf - Accepted Version - Requires a PDF viewer. Download (2391Kb) | Preview |
Official URL: http://dx.doi.org/10.1158/1078-0432.CCR-16-1692
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: | Journal Article | ||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Computer Science | ||||||
Library of Congress Subject Headings (LCSH): | Cancer -- Treatment, Melanoma, Lymphocytes | ||||||
Journal or Publication Title: | Clinical Cancer Research | ||||||
Publisher: | American Association for Cancer Research | ||||||
ISSN: | 1078-0432 | ||||||
Official Date: | 5 July 2017 | ||||||
Dates: |
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Volume: | 23 | ||||||
Number: | 19 | ||||||
Page Range: | pp. 5779-5788 | ||||||
DOI: | 10.1158/1078-0432.CCR-16-1692 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||
Date of first compliant deposit: | 14 July 2017 | ||||||
Date of first compliant Open Access: | 5 July 2018 | ||||||
Funder: | Landsforeningen til kræftens bekæmpelse (Denmark), Region hovedstaden [The Capital Region of Demnark], Aase og Ejnar Danielsens Fond [Aase and Ejnar Danielsen Foundation] |
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