BACH2 (BTB Domain And CNC Homolog 2)

Immune checkpoint inhibitors cause elevated cardiac injuries in humans and mice ICIs cause myocyte pyroptosis and cardiotoxicity not via the adaptive immune system BACH2 ameliorates ICIs-induced pyroptosis through transcriptionally promoting GRSF1. Lipoic acid as a transcriptional inducer of BACH2 suppresses ICIs-induced cardiotoxicity.

Through interrogation of clinical CAR products, we further found an association between BACH2 activity and clinical outcomes in patients with leukemia. These data identify a central function for BACH2 in regulating CAR T cell efficacy.

Temporal and quantitative induction of BACH2 expression in CAR T cells during manufacturing using chemical switches fine-tunes the degree of stemness and imprints greater control of solid tumors. Together, these data show that BACH2 dosage defines stemness hierarchy in CAR T cells and can be temporally and tunably controlled to optimize differentiation and antitumor efficacy.

Similarly, dose optimization enables effective deployment of quiescence factor FOXO1. Thus, quantitative control of gene payloads yields qualitative effects on outcome with implications for quiescence factor deployment in cell therapy.

While no causal relationship between MS liability and cancer risk was identified, shared genetic effects highlight potential biological mechanisms linking immune regulation in MS and cancer risk. The observed antagonistic pleiotropy, where genetic variants increase MS risk but decrease cancer susceptibility, mirrors patterns seen in autoimmunity and infection.

Additionally, the review discusses the recent findings on the potential mechanisms elucidating the dynamic roles of BACH2 associated with B and/or plasma cells. Lastly, the review explores the involvement of aberrant function of BACH2 as an exacerbating factor for the onset of B-cell malignancies, along with its possible oncogenic roles and its network as a therapeutic target.

In preclinical tumor models, PLP treatment improves the efficacy of anti-programmed death receptor 1 (PD-1) antibody therapy. Thus, our study reveals a pathway that preserves T cell functional stemness-like phenotypes to drive the acquisition of antitumor immunity, highlighting the clinical potential of vitamin B6/PLP-enhanced T cell function strategies in cancer immunotherapy.

High-risk patients exhibited poor survival, enhanced immune infiltration, and potential sensitivity to AKT inhibitors, with several drugs, including gefitinib and paclitaxel, identified as promising candidates. Additional prognostic genes (DFFB, PSMB6, GLP1R, HDAC9, BACH2) displayed expression patterns largely consistent across HPA, TCGA, and RT-qPCR, with minor discrepancies likely due to sample size. This study integrates multi-omics and deep learning with experimental validation, providing insights into programmed cell death regulation and offering robust biomarkers and therapeutic targets for GC.

Pharmacological inhibition of CXCR2 using SB225002, a selective small-molecule antagonist, was evaluated to determine its effects on cell growth, colony formation, apoptosis, and cell cycle progression in different NB cell lines...This study provides strong evidence for elucidating CXCR2-targeted therapies as an attractive treatment option for NB. These findings support the development of CXCR2-targeted therapies for high-risk NB.

Our data suggest that BACH2, a candidate transcription factor implicated in aging-mediated functional decline of DG neurons, potentially regulates genes associated with synaptic plasticity, cell death, and inflammation during aging. Taken together, our single-nucleus multiome analysis reveals potential cell type-specific regulators involved in the aging of neurons and glial cells.

Genes like BCL6 and BACH2 tied to these conversions are downregulated faster by JQ1, a super-enhancer-disrupting anti-cancer agent...Super-silencer repression depends on CpG content: CpG-rich elements block promoter-enhancer contacts; CpG-poor - inhibit looping. These findings highlight super-silencers' key role in B-cell regulation and suggest their alteration may be a primary factor of B-cell carcinogenesis.

Chemically inducing temporal BACH2 activation during manufacture of GD2 CAR T cells imprinted greater antitumor immunity against solid tumor after infusion. Together, we show that BACH2 dosage establishes the hierarchy of stem-like CAR T cells and can be temporally and tunably controlled in CAR T cells to optimize differentiation and antitumor immunity.