High-throughput Screening of Human Tumor Antigen-specific CD4 T Cells, Including Neoantigen-reactive T Cells.

Details

Serval ID
serval:BIB_99ED3D648751
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
High-throughput Screening of Human Tumor Antigen-specific CD4 T Cells, Including Neoantigen-reactive T Cells.
Journal
Clinical cancer research
Author(s)
Costa-Nunes C., Cachot A., Bobisse S., Arnaud M., Genolet R., Baumgaertner P., Speiser D.E., Sousa Alves P.M., Sandoval F., Adotévi O., Reith W., Protti M.P., Coukos G., Harari A., Romero P., Jandus C.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
15/07/2019
Peer-reviewed
Oui
Volume
25
Number
14
Pages
4320-4331
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Characterization of tumor antigen-specific CD4 T-cell responses in healthy donors and malignant melanoma patients using an in vitro amplified T-cell library screening procedure.
A high-throughput, human leukocyte antigen (HLA)-independent approach was used to estimate at unprecedented high sensitivity level precursor frequencies of tumor antigen- and neoantigen-specific CD4 T cells in healthy donors and patients with cancer. Frequency estimation was combined with isolation and functional characterization of identified tumor-reactive CD4 T-cell clones.
In healthy donors, we report frequencies of naïve tumor-associated antigen (TAA)-specific CD4 T cells comparable with those of CD4 T cells specific for infectious agents (Tetanus toxoid). Interestingly, we also identified low, but consistent numbers of memory CD4 T cells specific for several TAAs. In patients with melanoma, low frequencies of circulating TAA-specific CD4 T cells were detected that increased after peptide-based immunotherapy. Such antitumor TAA-specific CD4 T-cell responses were also detectable within the tumor-infiltrated tissues. TAA-specific CD4 T cells in patients displayed a highly polyfunctional state, with partial skewing to Type-2 polarization. Finally, we report the applicability of this approach to the detection and amplification of neoantigen-specific CD4 T cells.
This simple, noninvasive, high-throughput screening of tumor- and neoantigen-specific CD4 T cells requires little biologic material, is HLA class II independent and allows the concomitant screening for a large number of tumor antigens of interest, including neoantigens. This approach will facilitate the immunomonitoring of preexisting and therapy-induced CD4 T-cell responses, and accelerate the development of CD4 T-cell-based therapies.
Pubmed
Web of science
Create date
03/05/2019 16:10
Last modification date
21/08/2019 5:32
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