siRNA-Mediated B7H7 Knockdown in Gastric Cancer Lysate-Loaded Dendritic Cells Amplifies Expansion and Cytokine Secretion of Autologous T Cells

Biomedicines, Год журнала: 2023, Номер 11(12), С. 3212 - 3212

Опубликована: Дек. 4, 2023

Gastric cancer, ranked as the fifth most common cancer worldwide, presents multiple treatment challenges. These obstacles often arise due to stem cells, which are associated with recurrence, metastasis, and drug resistance. While dendritic cell (DC)-based immunotherapy has shown promise a therapeutic strategy, its efficacy can be limited by tumor microenvironment certain inhibitory immune checkpoint molecules, such B7H7. SiRNA-medicated knockdown of B7H7 in lysate-pulsed DCs increase cytokine secretion autologous T lymphocyte expansion. This study aimed evaluate impact suppression gastric on stimulatory potential CD3+ lymphocytes.Peripheral blood mononuclear cells (PBMCs) were isolated monocytes obtained; then, they differentiated immature (iDCs) GM-CSF IL-4. Tumor lysates from human lines harvested, iDCs transformed into mature (mDCs) stimulating lysate lipopolysaccharide. B7H7-siRNA was delivered mDCs using electroporation, gene silencing efficiency assessed. The phenotypic characteristics iDCs, mDCs, B7H7-silenced evaluated specific surface markers, an inverted light microscope, flow cytometry. via magnetically activated sorting. They labeled CFSE dye co-cultured their ability induce T-cell proliferation. proliferation assessed concentration TGF-β, IL-4, IFN-γ secreted supernatant investigate secretory activity cells.Transfection siRNA performed optimal conditions, transfection effectively reduced mRNA expression dose-dependent manner. SiRNA-mediated enhanced maturation activation DCs, demonstrated increased CD11c, CD86, CD40. Co-culture experiments revealed that had more capacity compared non-transfected mDCs. production patterns also altered. Upon examining levels released co-culture supernatant, we found resulted rise IL-4 reduction TGF-β not transfected.The suppressing significantly enhances when exposed lysate. substantially promote Consequently, inhibiting may offer practical strategy enhance initiate responses improve effectiveness DC-based therapy for patients.

Язык: Английский

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Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD)

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Март 29, 2024

Abstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness neoadjuvant immunotherapy among NSCLC COPD versus without and explore potential mechanistic links. Patients methods receiving surgery at Shanghai Pulmonary Hospital between November 2020 January 2023 were reviewed. assessment immunotherapy’s conducted based on major pathologic response (MPR). gene expression profile investigated RNA sequencing data. Immune proportions examined using flow cytometry. association expression, immune cells, validated immunohistochemistry single-cell Results A total 230 who received analyzed, including 60 (26.1%) COPD. Multivariate logistic regression demonstrated that predictor for MPR after [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. showed down-regulation HERV–H LTR-associating protein 2 (HHLA2), which an checkpoint molecule, HHLA2 low group enrichment CD8 + CD103 tissue-resident memory T cells (TRM) compared high (11.9% vs. 4.2%, 0.013). Single-cell analysis revealed TRM group. Similarly, exhibited higher proportion 4.6%, 0.040). Conclusions identified as type immunotherapy, offering new perspective multimodality treatment patient population. Down-regulated might improve rate owing TRM. Trial registration Approval collection utilization clinical samples granted Ethics Committee (Approval number: K23-228).

Язык: Английский

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Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Июнь 27, 2024

Abstract Distinct Natural Killer (NK)-like CD57 + and PD-1 CD8 exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins relationships between these types are poorly understood. Here we show that while Tex epigenetically similar, cells display unique increased chromatin accessibility of inhibitory Cell Immunoglobulin-like Receptor (iKIR) other NK genes. also reciprocal expression Inhibitory Receptors (IRs) iKIRs accompanied by Tcf1 Tbet transcription factor target sites, respectively. unappreciated gene heterogeneity share clonal with Tex, differentiating along four interconnected lineage trajectories: Tex-PD-1 , Tex-CD57 Tex-Branching, Tex-Fluid. Our findings demonstrate new Tex-like human disease suggest modulating common precursor may enhance treatment.

Язык: Английский

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An integrated pan-cancer assessment of prognosis, immune infiltration, and immunotherapy response for B7 family using multi-omics data

Life Sciences, Год журнала: 2024, Номер 353, С. 122919 - 122919

Опубликована: Июль 20, 2024

Язык: Английский

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