These findings suggest T cell depletion via IL7-IL7R signaling may drive prostate cancer progression, offering novel therapeutic insights.

In animal models, compared with conventional CAR-T cells, B7H3-IL7R-S CAR-T cells suppressed tumor growth and prolonged overall survival. Our study demonstrated the therapeutic potential of IL7Rα-incorporating CAR-T cells for glioblastoma treatment, suggesting a promising strategy for augmenting the effectiveness of CAR-T cell therapy.

IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.

P1, N=54, Completed, GlaxoSmithKline | Recruiting --> Completed | Trial completion date: Jun 2023 --> Oct 2023 | Trial primary completion date: Jun 2023 --> Oct 2023

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.

Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL7/IL7R and IL15/IL15R as pairs of chemokines and receptors with potential roles in promoting chemotactic migration of breast cancer cells with mesenchymal properties towards the lymphatics. The results demonstrate the capacity of TGFβ1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells and warrant further studies to explore the roles of IL7 and IL15 in promoting lymph metastasis of breast cancer.

In conclusion, GPC3-7-19-CAR-T cells achieved antitumor effects superior to those of conventional GPC3-CAR-T cells by reconstructing the TME induced by the dominant CD4 T and CD8 T cell subsets. Most importantly, GPC3-7-19-CAR-T cells exhibited good safety and antitumor efficacy in HCC patients in the clinic. ► Novel GPC3-7-19-CAR-T cells designed with mediate level of IL-7 secretion and high level of CCL19 secretion, which could recruit more mature DCs to assist killing on GPC3HCCs. ►DC cells recruited by CCL19 could interact with CD4 T cells and promote the differentiation of CD4T cells into CD4T and CD8T subsets, leading a better anti-tumor effect on GPC3HCCs. ►Compared with conventional GPC3-CAR-T, GPC3-7-CCL19-CAR-T cells could reverse tumor immunosuppressive microenvironment by reducing PMN-MDSC and Treg cell infiltration.

, fludarabine dose from 25 to 30 mg/m 2, and cyclophosphamide dose from 250 to 500 mg/m 2). Analyses are ongoing to characterize associations of patient characteristics, product differences, and circulating immune cell subsets with changes in cytokine profile over time. Further studies are warranted to validate our findings in a larger data set.

Furthermore, these peptides showed synergistic cytotoxicity with Sorafenib in drug-resistant HCC cells co-overexpressing both IL7 and MAL2. Our studies suggest that targeting autophagy may be a novel strategy to overcome IL7/MAL2-mediated Sorafenib resistance in HCC.

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted-therapies. Altogether, this study provides valuable information to optimize translation of JAKi and venetoclax to clinics for T-ALL patients with relapse who need therapeutics to bridge to transplant. This treatment protocol may benefit to a larger group of patients who may be selected with an easily applicable flow-cytometry-based companion test. IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T- ALL patients eligible to JAKi up to nearly ~70% of T-ALL.

Conversely, mutants were more sensitive to venetoclax than expressers. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.