Clinically-Relevant Rapamycin Treatment Regimens Enhance CD8+ Effector Memory T Cell Function In The Skin and Allow their Infiltration into Cutaneous Squamous Cell Carcinoma

Oncoimmunology
Ji-Won JungJames William Wells

Abstract

Patients receiving immunosuppressive drugs to prevent organ transplant rejection exhibit a greatly increased risk of developing cutaneous squamous cell carcinoma (SCC). However, not all immunosuppressive drugs confer the same risk. Randomised, controlled trials demonstrate that switching renal transplant recipients receiving calcineurin inhibitor-based therapies to mammalian target of rapamycin (mTOR) inhibitors results in a reduced incidence of de novo SSC formation, and can even result in the regression of pre-existing premalignant lesions. However, the contribution played by residual immune function in this setting is unclear. We examined the hypotheses that mTOR inhibitors promote the enhanced differentiation and function of CD8+ memory T cells in the skin. Here, we demonstrate that the long-term oral administration of rapamycin to achieve clinically-relevant whole blood drug target thresholds, creates a "low rapamycin dose" environment in the skin. While both rapamycin and the calcineurin inhibitor tacrolimus elongated the survival of OVA-expressing skin grafts, and inhibited short-term antigen-specific CD8+ T cell responses, rapamycin but not tacrolimus permitted the statistically significant infiltration of CD8+ effector...Continue Reading

References

Nov 1, 1974·Journal of the National Cancer Institute·M L Kripke
Oct 6, 1999·British Journal of Clinical Pharmacology·Y BöttigerC G Groth
Nov 2, 2002·The British Journal of Dermatology·H M RamsayP N Harden
Jun 18, 2003·European Journal of Immunology·Hiroaki AzukizawaSatoshi Itami
Apr 1, 2005·The New England Journal of Medicine·Giovanni StalloneGiuseppe Grandaliano
Aug 13, 2005·The Journal of Dermatological Treatment·Mark NaylorJoyce M Rico
Jan 3, 2006·Transplantation Proceedings·A Gutiérrez-DalmauJ M Campistol
Dec 13, 2006·International Immunopharmacology·Maria BoratyńskaMarian Klinger
Jan 9, 2007·The Journal of Allergy and Clinical Immunology·James W WellsAlistair Noble
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yan ZhengJonathan D Powell
Apr 13, 2007·Transplant Infectious Disease : an Official Journal of the Transplantation Society·N BabelP Reinke
Feb 23, 2008·The American Journal of Pathology·Sabita RanaGary Mark Halliday
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·James W WellsAlistair Noble
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mehmet O KilincNejat K Egilmez
Jun 23, 2009·Nature·Koichi ArakiRafi Ahmed
Jan 20, 2010·Clinics in Dermatology·Diamant Thaçi, Rebekka Salgo
Feb 4, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R SalgoE H Scheuermann
Sep 8, 2011·The British Journal of Dermatology·L FeldmeyerJ Hafner
Mar 17, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S B CampbellG R Russ
Jul 27, 2012·The New England Journal of Medicine·Sylvie EuvrardUNKNOWN TUMORAPA Study Group
Aug 11, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher H EvansJames W Wells
Oct 20, 2012·Nature Reviews. Immunology·Susan M Kaech, Weiguo Cui
Jan 30, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Judith M Hoogendijk-van den AkkerJohan W de Fijter
Jul 30, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan T SowellAmanda L Marzo
Jan 24, 2015·Pharmacogenomics·Michael T BurkeChristine E Staatz
May 19, 2016·Immunity·Margaret K CallahanJedd D Wolchok
May 20, 2016·Cancer Research·Laurent BeziaudOlivier Adotévi
Feb 12, 2017·Cell·Wendell A Lim, Carl H June
Jul 15, 2017·Transplantation Direct·Michael Thomas BurkeJames William Wells

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Citations

Oct 7, 2019·Aging·Mikhail V Blagosklonny
Jun 15, 2021·Frontiers in Cellular and Infection Microbiology·Barbara Ferri MoraschiJosé Ronnie C Vasconcelos
Apr 14, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Christine HoeslMaik Dahlhoff

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Methods Mentioned

BETA
transgenic
scraping
FACS
flow cytometry

Software Mentioned

GraphPad
FlowJo
GraphPad Prism

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