Optimized combinatorial pMHC class II multimer labeling for precision immune monitoring of tumor-specific CD4 T cells in patients.

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State: Public
Version: author
License: CC BY-NC 4.0
Serval ID
serval:BIB_EBA81BA22D33
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Optimized combinatorial pMHC class II multimer labeling for precision immune monitoring of tumor-specific CD4 T cells in patients.
Journal
Journal for immunotherapy of cancer
Author(s)
Rockinger G.A., Guillaume P., Cachot A., Saillard M., Speiser D.E., Coukos G., Harari A., Romero P.J., Schmidt J., Jandus C.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Publication state
Published
Issued date
05/2020
Peer-reviewed
Oui
Volume
8
Number
1
Pages
e000435
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
With immunotherapy gaining increasing approval for treatment of different tumor types, scientists rely on cutting edge methods for the monitoring of immune responses and biomarker development in patients. Due to the lack of tools to efficiently detect rare circulating human tumor-specific CD4 T cells, their characterization in patients still remains very limited.
We have used combinatorial staining strategies with peptide major histocompatibility complex class II (pMHCII) multimer constructs of different alleles to establish an optimized staining procedure for in vitro and direct ex-vivo visualization of tumor-specific CD4 T cells, in patient samples. Furthermore, we have generated reversible multimers to achieve optimal cell staining and yet disassemble prior to in vitro cell expansion, thus preventing activation induced cell death.
We observed a vastly improved detection of tumor-specific, viral-specific and bacterial-specific cells with our optimization methods compared with the non-optimized staining procedure. By increasing the variety of fluorochromes used to label the pMHCII multimers, we were also able to increase the parallel detection of different specificities within one sample, including antigen-specific CD8 T cells. A decrease in cell viability was observed when using the full optimization method, but this was mitigated by the removal of neuraminidase and the use of reversible multimers.
This new optimized staining procedure represents an advance toward better detection and analysis of antigen-specific CD4 T cells. It should facilitate state-of-the art precision monitoring of tumor-specific CD4 T cells and contribute to accelerate the use and the targeting of these cells in cancer immunotherapy.
Keywords
immunology, oncology
Pubmed
Web of science
Open Access
Yes
Create date
01/12/2020 11:11
Last modification date
17/06/2021 6:35
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