STING Activation Reverses Lymphoma-Mediated Resistance to Antibody Immunotherapy

Cancer Research
Lekh N DahalStephen A Beers

Abstract

Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM), which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy. Both STINGa and TLRa induced cytokine release, modulated FcγR expression, and augmented mAb-mediated tumor cell phagocytosis in vitro However, only STINGa reversed the suppressive FcγR profile in vivo, providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma. Potent adjuvants like STINGa, which can improve FcγR activatory:inhibitory (A:I) ratios on TAM, are appealing candidates to reprogram TAM and curb tumor-mediated immunosuppression, thereby empowering mAb efficacy. Cancer Res; 77(13); 3619-31. ©2017 AACR.

References

Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Dec 3, 2005·Science·Falk Nimmerjahn, Jeffrey V Ravetch
Oct 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John P LeonardGeorge J Weiner
Apr 4, 2008·The New England Journal of Medicine·Manon van SetersTheo J M Helmerhorst
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Steve A BroomfieldAndrew J Currie
Jun 13, 2009·British Journal of Haematology·Jonathan W FriedbergArnold S Freedman
Apr 8, 2010·Cell·Bin-Zhi Qian, Jeffrey W Pollard
Jun 1, 2010·Immunity·Siamon Gordon, Fernando O Martinez
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joshua D BrodyRonald Levy
Jun 29, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Primo N LaraGiorgio Scagliotti
Sep 29, 2011·Nature·Dara L BurdetteRussell E Vance
Mar 23, 2012·Nature Reviews. Immunology·Dmitry I GabrilovichVincenzo Bronte
Nov 28, 2012·Molecules and Cells·Cha-Uk LeeMyung-Kwan Han
Mar 14, 2013·British Journal of Cancer·Z G FridlenderS M Albelda
Apr 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph ConlonKatherine A Fitzgerald
Sep 21, 2013·Nature Immunology·Thomas F GajewskiYang-Xin Fu
Jan 17, 2014·The Journal of Clinical Investigation·Nuray GülMarjolein van Egmond
Jun 12, 2014·Immunobiology·Daphne Y S VogelRobert H J Beelen
Jul 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ann L WhiteStephen A Beers
Oct 17, 2014·Immunological Reviews·Siamon GordonFernando Martinez Estrada
Mar 12, 2015·Trends in Immunology·Seng-Ryong WooThomas F Gajewski
Oct 2, 2015·Current Opinion in Pharmacology·Joachim L Schultze
Oct 27, 2015·Immunological Reviews·Lekh N DahalMark S Cragg
Oct 30, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alison L TuttMark S Cragg
Dec 19, 2015·Nature Immunology·Florent GinhouxSubhra K Biswas
Mar 10, 2016·Cancer Research·Chih-Hang Anthony TangChih-Chi Andrew Hu

❮ Previous
Next ❯

Citations

Jun 13, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Josh Sopp, Mark S Cragg
Jul 13, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lekh N DahalStephen A Beers
Apr 25, 2018·Frontiers in Immunology·Sandra IuresciaMonica Rinaldi
Nov 19, 2019·Experimental & Molecular Medicine·Tae Hyun Kang, Sang Taek Jung
Oct 20, 2017·Frontiers in Immunology·Michael J E MarshallMark S Cragg
May 2, 2019·Cancer Discovery·Chen LossosDavid M Weinstock
Feb 26, 2021·Frontiers in Immunology·Russell FoxallMark S Cragg
Jan 28, 2021·Molecular Cancer Research : MCR·Abdullah AlsufyaniLekh N Dahal
May 11, 2021·Frontiers in Immunology·Xao X TangNaohiko Ikegaki
Jun 27, 2021·NPJ Breast Cancer·Eileen E ParkesNiamh E Buckley
Jul 6, 2021·Biotechnology and Bioprocess Engineering : BBE·Seung Hyun Kang, Chang-Han Lee
Jul 21, 2021·International Journal of Molecular Sciences·Pedram Moeini, Paulina Niedźwiedzka-Rystwej
Apr 28, 2021·Cancer Research·Emma SaultersLekh N Dahal
Aug 17, 2021·Frontiers in Immunology·Mercedes Beatriz FuertesNorberto Walter Zwirner

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.