Imperial College London
Alternate

DR JAMES A HARKER

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Respiratory Science
 
 
 
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Contact

 

+44 (0)20 7594 3171j.harker

 
 
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Location

 

360Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Niogret:2021:10.1136/jitc-2020-002157,
author = {Niogret, J and Berger, H and Rebe, C and Mary, R and Ballot, E and Truntzer, C and Thibaudin, M and Derangère, V and Hibos, C and Hampe, L and Rageot, D and Accogli, T and Joubert, P and Routy, B and Harker, J and Vegran, F and Ghiringhelli, F and Chalmin, F},
doi = {10.1136/jitc-2020-002157},
journal = {Journal for ImmunoTherapy of Cancer},
title = {Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy},
url = {http://dx.doi.org/10.1136/jitc-2020-002157},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: T follicular helper cells (Tfh) are essential to shape B cell response during germinal center formation. Tfh accumulation has been reported in various human cancers, with positive or negative prognostic roles. However, the mechanisms explaining the accumulation of Tfh and their role in cancer remain obscure. METHODS: In vitro differentiated and mouse cell sorted Tfh phenotype was evaluated by flow cytometry and quantitative PCR (qPCR). Antitumor effect of Tfh was evaluated by adoptive transfer in different tumor-bearing mice models. The involvement of immune cells, cytokines and chemokines was evaluated, using depleting antibodies. Chemokines and cytokines expression and production were evaluated by qPCR and ELISA. In human, the impact of immune cells and chemokines on survival was evaluated by analyzing transcriptomic data from public databases and from our own patient cohorts. RESULTS: In this study, we show that Tfh exert an antitumor immune effect in a CD8+-dependent manner. Tfh produce interleukin-21, which sustains proliferation, viability, cytokine production and cytotoxic functions of exhausted T cells. The presence of Tfh is required for efficacy of antiprogrammed cell death ligand-1 therapy. Tfh accumulate in the tumor bed and draining lymph nodes in different mouse cancer models. This recruitment is due to the capacity of transforming growth factor β to drive Chemokine (C-X-C motif) Ligand 13 expression, a chemoattractant of Tfh, by intratumor CD8+ T cells. Accumulation of Tfh and exhausted CD8+ T cells predicts cancer outcome in various cancer types. In patients treated with anti-programmed cell death-1 mAb, accumulation of Tfh and CD8+ at the tumor site is associated with outcome. CONCLUSION: This study provides evidence that CD8+/Tfh crosstalk is important in shaping antitumor immune response generated by immunotherapy.
AU  - Niogret,J
AU  - Berger,H
AU  - Rebe,C
AU  - Mary,R
AU  - Ballot,E
AU  - Truntzer,C
AU  - Thibaudin,M
AU  - Derangère,V
AU  - Hibos,C
AU  - Hampe,L
AU  - Rageot,D
AU  - Accogli,T
AU  - Joubert,P
AU  - Routy,B
AU  - Harker,J
AU  - Vegran,F
AU  - Ghiringhelli,F
AU  - Chalmin,F
DO  - 10.1136/jitc-2020-002157
PY  - 2021///
SN  - 2051-1426
TI  - Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy
T2  - Journal for ImmunoTherapy of Cancer
UR  - http://dx.doi.org/10.1136/jitc-2020-002157
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34103351
UR  - http://hdl.handle.net/10044/1/89627
VL  - 9
ER  -
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