Cytokine signaling in chimeric antigen receptor T-cell therapy

Article Immunology

STAT3 regulates CD8+ T cell differentiation and functions in cancer and acute infection

Qinli Sun et al.

Summary: Sun et al. discovered that STAT3, activated by IL-10 and IL-21, plays crucial roles in the terminal differentiation of effector CD8(+) T cells in cancer and acute infection. STAT3 enhances effector functions and survival of T-ex(term) cells in the tumor microenvironment, leading to improved tumor control. It transcriptionally promotes effector function-related genes and collaborates with BATF and IRF4 to mediate chromatin activation at effector gene loci.

JOURNAL OF EXPERIMENTAL MEDICINE (2023)

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Article Immunology

Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion

Avishai Shemesh et al.

Summary: Low IL-12 concentrations are sufficient for the expansion of human NK cells through innate-activating NK receptor-orchestrated differential IL-12 signalling. This study demonstrates that activating NK receptor stimulation promotes differential IL-12 signalling, leading to human NK cell expansion.

JOURNAL OF EXPERIMENTAL MEDICINE (2022)

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Article Medicine, General & Internal

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma

Nikhil C. Munshi et al.

Summary: The phase 2 study confirmed the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma, with a majority of patients achieving responses and 26% achieving MRD-negative status. Despite the high response rate, almost all patients experienced grade 3 or 4 toxic effects, including hematologic toxic effects and cytokine release syndrome.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Immunology

Therapeutic Potential of TNFα and IL1β Blockade for CRS/ICANS in CAR-T Therapy via Ameliorating Endothelial Activation

Yunshuo Chen et al.

Summary: Therapeutic blockade of TNF alpha and IL1 beta signaling, along with the use of FAK inhibitor, effectively reduced endothelial activation induced by CAR-T cells, tumor cells, and myeloid cells. Adalimumab and anti-IL1 beta antibody showed synergistic effects in preventing endothelial activation induced by CAR-T cells, tumor cells, and myeloid cells. These results suggest that TNF alpha and IL1 beta blockade could be a potential therapeutic approach for CRS and neurotoxicity associated with CAR-T therapy.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Medicine, Research & Experimental

BET bromodomain protein inhibition reverses chimeric antigen receptor extinction and reinvigorates exhausted T cells in chronic lymphocytic leukemia

Weimin Kong et al.

Summary: CAR T cell therapy has shown remarkable anti-tumor responses in some B cell malignancies, but there are patients who do not respond due to T cell deficiencies affecting the expansion, persistence, and effector function of CAR T cells. Longitudinal immune profiling identified phenotypic and pharmacodynamic changes in CAR T cells in chronic lymphocytic leukemia patients, revealing that CAR T cell failure may be associated with preexisting T cell defects or acquired dysfunction. Bet epigenetic readers modulation could potentially enhance the efficacy of cell-based immunotherapies.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Review Immunology