Biomaterial Database

STING Activation Reverses Lymphoma-Mediated Resistance to Antibody Immunotherapy. 2017

Lekh N Dahal, and Lang Dou, and Khiyam Hussain, and Rena Liu, and Alexander Earley, and Kerry L Cox, and Salome Murinello, and Ian Tracy, and Francesco Forconi, and Andrew J Steele, and Patrick J Duriez, and Diego Gomez-Nicola, and Jessica L Teeling, and Martin J Glennie, and Mark S Cragg, and Stephen A Beers

Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.

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.

UI	MeSH Term	Description	Entries
D007116	Immunization, Passive	Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).	Convalescent Plasma Therapy,Immunoglobulin Therapy,Immunotherapy, Passive,Normal Serum Globulin Therapy,Passive Antibody Transfer,Passive Transfer of Immunity,Serotherapy,Passive Immunotherapy,Therapy, Immunoglobulin,Antibody Transfer, Passive,Passive Immunization,Therapy, Convalescent Plasma,Transfer, Passive Antibody
D008223	Lymphoma	A general term for various neoplastic diseases of the lymphoid tissue.	Germinoblastoma,Lymphoma, Malignant,Reticulolymphosarcoma,Sarcoma, Germinoblastic,Germinoblastic Sarcoma,Germinoblastic Sarcomas,Germinoblastomas,Lymphomas,Lymphomas, Malignant,Malignant Lymphoma,Malignant Lymphomas,Reticulolymphosarcomas,Sarcomas, Germinoblastic
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D017452	Receptors, IgG	Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).	Antigens, CD16,Antigens, CD32,Antigens, CD64,CD16 Antigens,CD32 Antigens,CD64 Antigen,CD64 Antigens,Fc Gamma Receptor,Fc Receptors, gamma,Fc gamma Receptors,IgG Receptor,IgG Receptors,Leu-11 Antigen,Receptors, Fc gamma,gamma Fc Receptor,gamma Fc Receptors,CD 16 Antigens,CD 32 Antigens,CD 64 Antigens,CDw32 Antigens,Fc gamma RI,Fc gamma RII,Fc gamma RIII,Immunoglobulin G Receptor,Leu-11 Antigens,Antigen, CD64,Antigen, Leu-11,Antigens, CD 16,Antigens, CD 32,Antigens, CD 64,Antigens, CDw32,Antigens, Leu-11,Fc Receptor, gamma,Gamma Receptor, Fc,Leu 11 Antigen,Leu 11 Antigens,Receptor, Fc Gamma,Receptor, IgG,Receptor, Immunoglobulin G,Receptor, gamma Fc,Receptors, gamma Fc,gamma RI, Fc,gamma RII, Fc,gamma RIII, Fc,gamma Receptors, Fc
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus