Integrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function

Background
The success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies has not yet translated into long-term elimination of solid tumors indicating the need for adequately tuning CAR T cell functionality.

Methods
We l…

ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis

Background
The failure of conventional therapies and the propensity for recurrence and metastasis make triple-negative breast cancer (TNBC) a formidable challenge with grim prognoses and diminished survival rates. Immunotherapy, including immune check…

Magnitude of antigen-specific T-cell immunity the month after completing vaccination series predicts the development of long-term persistence of antitumor immune response

Background
For best efficacy, vaccines must provide long-lasting immunity. To measure longevity, memory from B and T cells are surrogate endpoints for vaccine efficacy. When antibodies are insufficient for protection, the immune response must rely on …

Bendamustine-rituximab elicits dual tumoricidal and immunomodulatory responses via cGAS-STING activation in diffuse large B-cell lymphoma

Background
Bendamustine–rituximab (BR) therapy stands out as a promising alternative for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating notable efficacy when conventional regimens pose challenges. Despite its clinical…

Neoantigen architectures define immunogenicity and drive immune evasion of tumors with heterogenous neoantigen expression

Background
Intratumoral heterogeneity (ITH) and subclonal antigen expression blunt antitumor immunity and are associated with poor responses to immune-checkpoint blockade immunotherapy (ICB) in patients with cancer. The underlying mechanisms however t…

Depletion of conventional CD4+ T cells is required for robust priming and dissemination of tumor antigen-specific CD8+ T cells in the setting of anti-CD4 therapy

Background
Overcoming immune suppression is a major barrier to eliciting potent CD8+ T cell responses against cancer. Treatment with anti-CD4 monoclonal antibody is an effective means for eliminating CD4+Foxp3+ regulatory (Treg) cells in preclinical m…

Body mass index and type 2 diabetes mellitus as metabolic determinants of immune checkpoint inhibitors response in melanoma

Background
Immune checkpoint inhibitors (ICIs) have improved survival outcomes in melanoma. Studies exploring the correlations between body mass index (BMI), type 2 diabetes (T2DM) and the outcomes of ICI treatment have yielded inconsistent results. I…

TMED inhibition suppresses cell surface PD-1 expression and overcomes T cell dysfunction

Background
Blockade of the programmed cell death protein 1 (PD-1) immune checkpoint (ICB) is revolutionizing cancer therapy, but little is known about the mechanisms governing its expression on CD8 T cells. Because PD-1 is induced during activation of…

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