OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function
| Autor: | Andrew D. Weinberg, Amy E. Moran, Fanny Polesso, Minhaz Sarker, Susan E. Murray |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Agonist
Regulatory T cell medicine.drug_class Antibodies Neoplasm medicine.medical_treatment T cell Immunology chemical and pharmacologic phenomena Mice Transgenic Biology CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory 03 medical and health sciences Mice 0302 clinical medicine Immune system Cell Line Tumor Neoplasms medicine Immunology and Allergy Cytotoxic T cell Animals FOXP3 hemic and immune systems Immunotherapy Receptors OX40 Neoplasm Proteins Granzyme B Gene Expression Regulation Neoplastic medicine.anatomical_structure Cancer research Cytokines 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 203(7) |
| ISSN: | 1550-6606 |
| Popis: | OX40 is a costimulatory molecule from the TNFR family. In mice, it is expressed on Foxp3+ regulatory T cells (Tregs) constitutively and on conventional CD4 (Tconv) and CD8 T cells after Ag encounter. OX40 agonists are in clinical development to enhance antitumor immune responses, and one proposed mechanism of action is loss of Treg suppressive function. Studies have postulated that agonist OX40 therapy can impair Treg suppressive function. Using tools developed since the initial studies were published, we evaluated a direct effect of OX40 agonism on Treg function. We conclude that OX40 agonist Abs do not intrinsically impair Treg function but rather enhance Tconv cell IL-2 production, increasing Treg and Tconv cell proliferation. OX40-stimulated Tregs retain suppressive function, but also gain IFN-γ, TNF-α, and granzyme B expression. These data help resolve mechanistic questions regarding OX40 agonist immunotherapy and thus are relevant to developing combination therapies that target distinct T cell functions. |
| Databáze: | OpenAIRE |
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