Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade.

Patients Treated with CTLA-4 Blockade Antitumor Responses and Autoimmunity in Analysis of the Cellular Mechanism of

Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function.

PURPOSE Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4(+) T cell numbers and function. We have previously shown that increased regulatory T cell (T(reg)) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic...

The ICOS/ICOSL pathway is required for optimal antitumor responses mediated by anti-CTLA-4 therapy.

The anti-CTL-associated antigen 4 (anti-CTLA-4) antibody ipilimumab is the first agent to show improved survival in a randomized phase III trial that enrolled patients with metastatic melanoma. Studies are ongoing to identify mechanisms that elicit clinical benefit in the setting of anti-CTLA-4 therapy. We previously reported that treated patients had an increase in the frequency of T cells exp...

Microenvironment and Immunology The ICOS/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti–CTLA-4 Therapy

The anti–CTL-associated antigen 4 (anti–CTLA-4) antibody ipilimumab is the first agent to show improved survival in a randomized phase III trial that enrolled patients with metastatic melanoma. Studies are ongoing to identify mechanisms that elicit clinical benefit in the setting of anti–CTLA-4 therapy. We previously reported that treated patients had an increase in the frequency of T cells exp...

Combination therapy of established tumors by antibodies targeting immune activating and suppressing molecules.

The blockade of immune suppression against antitumor responses is a particularly attractive strategy when combined with agents that promote tumor-specific CTLs. In this study, we have attempted to further improve the CTL induction and potent antitumor efficacy of a combination mAb-based therapy (termed "trimAb therapy") that comprises tumor cell death-inducing anti-death receptor 5 mAb and immu...