Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment

Nature Communications
Kyun-Do KimMinsoo Kim

Abstract

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp3+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites.

References

Sep 1, 1987·The Journal of Experimental Medicine·H Takayama, M V Sitkovsky
Aug 24, 1999·Immunology and Cell Biology·C KoniarasA M Lew
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jason S GoldAlan N Houghton
Aug 20, 2003·The Journal of Experimental Medicine·Willem W OverwijkNicholas P Restifo
Dec 30, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mei-Ling ChenKhashayarsha Khazaie
Mar 25, 2006·Nature Reviews. Immunology·Weiping Zou
May 2, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cor H J LamersEgbert Oosterwijk
Aug 22, 2006·Nature·Murali PrakriyaPatrick G Hogan
Dec 1, 2006·Annual Review of Immunology·Gabriel A RabinovichEduardo M Sotomayor
Dec 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gaynor J BatesAlison H Banham
Feb 13, 2007·The Journal of Biological Chemistry·Yousang GwackAnjana Rao
Apr 19, 2007·Biochemistry·Raji E JosephAmy H Andreotti
Jun 6, 2007·The Journal of Clinical Investigation·Carl H June
Sep 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephen H WrzesinskiRichard A Flavell
Mar 21, 2008·Nature Reviews. Cancer·Steven A RosenbergMark E Dudley
Jul 12, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Giuseppe PerroneFrancesco Graziano
Jan 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura StraussTheresa L Whiteside
Sep 17, 2009·Immunological Reviews·Arun T Pores-Fernando, Adam Zweifach
Aug 30, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyun-Do KimYousang Gwack
Dec 14, 2011·Journal of Molecular Cell Biology·Dat Q Tran
Jun 23, 2012·Cancer Research·Sid P Kerkar, Nicholas P Restifo
Jun 23, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shawn M JensenBernard A Fox
Oct 25, 2012·Annual Review of Medicine·Gregory LizéePatrick Hwu
Jan 12, 2013·Trends in Molecular Medicine·Gopal Murugaiyan, Bhaskar Saha
Dec 7, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyun-Do KimYousang Gwack
Feb 1, 2014·Nature Reviews. Immunology·Adrian Liston, Daniel H D Gray
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yuexin XuMinsoo Kim
May 9, 2014·The Journal of Clinical Investigation·Christian A BauerThorsten R Mempel
May 11, 2016·Molecular Therapy Oncolytics·Kheng NewickSteven M Albelda
Jan 1, 2015·ImmunoTargets and Therapy·Theresa L Whiteside

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Citations

Jan 26, 2018·The Journal of Physiology·Xiao ZhouMarkus Hoth
Aug 2, 2018·Small·Jiajia ZhouJean-Claude G Bünzli
Apr 8, 2020·Clinical and Experimental Immunology·S K SureshbabuS V Chiplunkar
Mar 4, 2020·Nature Communications·Armelle BohineustPhilippe Bousso
May 6, 2020·Cancer Reports·Louisiane PerrinBojana Gligorijevic
Oct 6, 2020·Frontiers in Immunology·María Tristán-ManzanoFrancisco Martin
Nov 2, 2019·Trends in Immunology·Morgane BoulchPhilippe Bousso
Oct 20, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Xinyuan ZhangKeyue Shen
Jun 19, 2021·Frontiers in Oncology·Thijs A van SchaikKhalid Shah
Jul 22, 2021·The FEBS Journal·Ling WuLiang Zhao

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Methods Mentioned

BETA
transgenic
PCR
FCS
flow cytometry
fluorescence-activated cell sorting
X-ray
transfection

Software Mentioned

Jmp
GraphPad Prism
SAS

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