Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells

Baumgaertner, Petra; Jandus, Camilla; Rivals, Jean-Paul; Derré, Laurent; Lövgren, Tanja; Baitsch, Lukas; Guillaume, Philippe; Luescher, Immanuel F; Berthod, Gregoire; Matter, Maurice; Rufer, Nathalie; Michielin, Olivier; Speiser, Daniel E (2012). Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells. International journal of cancer, 130(11), pp. 2607-17. Malden, Mass.: Wiley-Blackwell 10.1002/ijc.26297

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T-cells specific for foreign (e.g., viral) antigens can give rise to strong protective immune responses, whereas self/tumor antigen-specific T-cells are thought to be less powerful. However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients. Here we analyzed the functionality of these T-cells directly ex vivo, by multiparameter flow cytometry. The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways. Interestingly, high frequencies of functionally competent T-cells were induced irrespective of patient's age or gender. Finally, CD8 T-cell function correlated with disease-free survival. However, this result is preliminary since the study was a Phase I clinical trial. We conclude that human tumor-specific CD8 T-cells can reach functional competence in vivo, encouraging further development and Phase III trials assessing the clinical efficacy of robust vaccination strategies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Jandus, Camilla

ISSN:

0020-7136

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:18

Last Modified:

17 Mar 2015 19:23

Publisher DOI:

10.1002/ijc.26297

PubMed ID:

21796616

Web of Science ID:

000302013200014

URI:

https://boris.unibe.ch/id/eprint/5470 (FactScience: 210217)

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