OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function

Immunity without Affecting T Effector Suppressive Function Enhancing Tumor Blockade of CCL1 Inhibits T Regulatory Cell

Targeting the right regulatory T-cell population for tumor immunotherapy

Regulatory T cells (Tregs) that suppress tumor-specific T cell-mediated immune responses are the subject of an intense wave of investigation. We recently reported that a subset of Tregs, namely effector/memory CD25(low) cells, are responsible for suppressing high avidity tumor-specific T cells in mouse mammary tumors. Here, we discuss additional findings that clarify this mechanism of Treg-medi...

OX40 agonist immunotherapy expands tumor reactive CD8 T cells with a unique T cell receptor repertoire and synergizes with PDL-1 blockade to promote tumor regression

Previously, the field of tumor immunology has relied on T cell receptor (TCR) transgenic mice and model tumor antigens to study the T cell:tumor cell interaction. However, these models have limitations. Namely, they do not reflect the natural affinity, repertoire, or precursor frequency of tumor antigen-specific T cells. Using a novel TCR affinity tool, the Nur77GFP mouse, we have characterized...

Finding the right balance: aOX40 immunotherapy enhances effector T cell function without impairing regulatory T cells intrinsic suppressive capacity in mouse tumor models

Expression of the co-stimulatory molecule OX40 is induced after TCR ligation on conventional T cells and the importance of OX40 in promoting proliferation, effector function, and survival of activated T cells are illustrated in multiple disease models. Paradoxically, CD4+Foxp3+ regulatory T cells (Tregs) constitutively express OX40 in mice and OX40 receptor ligation by agonist antibodies has be...

Tumor-induced suppressive CD8+ T cells: implications for cancer immunotherapy

The immune system has the potential to be a powerful tool to destroy tumors; however despite ample evidence of endogenous anti-tumor immune responses in many patients, as well as years of immunotherapy development, truly effective immune-based therapies remain out of reach. We have previously shown that co-incubation of normal human T cells with various tumor lines can induce dysfunctional chan...