Combined triggering of dendritic cell receptors results in synergistic activation and potent cytotoxic immunity

The Journal of Immunology : Official Journal of the American Association of Immunologists
James W WellsAlistair Noble

Abstract

Elimination of malignant cells and intracellular infections involves collaboration between CTLs and Th1 inflammation. Dendritic cells drive this response via costimulation and cytokines. We have defined key signals required for the exponential expansion of specific CD8(+) T cells in vivo in mice. Immunization with two or more TLR agonists, anti-CD40, IFN-gamma, and surfactant were sufficient to drive unprecedented levels of CD8 response to peptide or protein Ag and highly polarized Th1 CD4 responses. CD40 signaling was required for CD8 expansion but could be provided by a concomitant CD4 Th response in place of anti-CD40. Triggering of these pathways activated migration and activation of myeloid and plasmacytoid dendritic cells and secretion of IL-12. Cross-presentation can thus be exploited to induce potent cytotoxic responses and long-term memory to peptide/protein Ags. When combined with a tumor-associated peptide from tyrosinase-related protein 2, our combined adjuvant approach effectively halted tumor growth in an in vivo melanoma model and was more effective than anti-CD40 and a single TLR agonist. Antitumor immunity was associated with long-lived effector memory CD8 cells specific for the naturally processed and presente...Continue Reading

References

Feb 3, 1997·The Journal of Experimental Medicine·M B BloomJ C Yang
Aug 6, 1999·Immunity·T KawaiS Akira
Nov 13, 1999·Science·K Murali-KrishnaR Ahmed
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M K MainiP C Beverley
Feb 2, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kathryn E FouldsHao Shen
Apr 12, 2002·Proceedings of the National Academy of Sciences of the United States of America·F Susan WongCharles A Janeway
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Evelyn RothHanspeter Pircher
Sep 5, 2002·European Journal of Immunology·Tobias MaurerHermann Wagner
Sep 26, 2002·Trends in Immunology·Thomas R Malek
Oct 18, 2002·Cancer Immunology, Immunotherapy : CII·Keith DredgeAngus G Dalgleish
Feb 21, 2003·Nature·Edith M JanssenStephen P Schoenberger
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Antje HeitHermann Wagner
Mar 10, 2004·The Journal of Experimental Medicine·Cory L AhonenRoss M Kedl
Mar 30, 2004·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Nicolas BurdinPhilippe Moingeon
Apr 9, 2004·The New England Journal of Medicine·Steven A Rosenberg
Jun 25, 2005·Current Drug Targets. Infectious Disorders·N Avrion Mitchison, Quentin Sattentau
Sep 27, 2005·Immunological Reviews·Kenneth L Rock, Lianjun Shen
Feb 24, 2006·Nature Reviews. Immunology·Marian R Neutra, Pamela A Kozlowski
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·James W RohrerJoseph H Coggin
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer A McWilliamsRoss M Kedl
Aug 26, 2006·Journal of Leukocyte Biology·Richard S Kornbluth, Geoffrey W Stone
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanyan LouGang Wang
Apr 25, 2007·Journal of Translational Medicine·Marc MansourPirouz Daftarian

❮ Previous
Next ❯

Citations

Oct 7, 2015·Cancer Immunology, Immunotherapy : CII·Susanne HofmannBarbara-Ann Guinn
Jul 7, 2015·Journal of Immunology Research·Gee Jun TyeMohd Nor Norazmi
Oct 18, 2018·Pathogens and Global Health·Min Han LewGee Jun Tye
Aug 24, 2010·Journal of Translational Medicine·Jochen T SchaeferCraig L Slingluff
Aug 7, 2012·European Journal of Immunology·Aurélie MoreauGiovanna Lombardi
Oct 7, 2015·Frontiers in Genetics·Nana H OvergaardGregers Jungersen
Sep 8, 2017·Frontiers in Oncology·Kyle M SchachtschneiderLawrence B Schook
Nov 13, 2019·Current Pharmaceutical Design·Nahid ZareianFarzin Farzaneh
Mar 19, 2016·European Journal of Immunology·Alistair NobleLynette Fairbanks
Feb 2, 2013·Cancer Gene Therapy·P LamB-A Guinn
Jun 21, 2020·Journal for Immunotherapy of Cancer·Victoria A BrentvilleLindy G Durrant
Aug 11, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher H EvansJames W Wells
Mar 22, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jan Ole KemnadeDavid M Spencer
Apr 4, 2021·Cancers·Dijana DjureinovicHarriet M Kluger
Nov 11, 2015·Veterinary Immunology and Immunopathology·Julien PujolLaurence Fiévez
Dec 14, 2011·The Journal of Investigative Dermatology·Filiberto Cedeno-LaurentCharles J Dimitroff

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Related Papers

Molecular Therapy : the Journal of the American Society of Gene Therapy
Alvaro LladserKarl Ljungberg
The Journal of Immunology : Official Journal of the American Association of Immunologists
Jakob LoschkoAnne B Krug
The Journal of Immunology : Official Journal of the American Association of Immunologists
William J MurphyRobert H Wiltrout
The Journal of Immunology : Official Journal of the American Association of Immunologists
M S Rolph, S H Kaufmann
© 2022 Meta ULC. All rights reserved