Istituto Europeo di Oncologia - IRCCS, Department of Experimental Oncology, Milan, Italy.
Published: August 2024
AI Article Synopsis
Article Abstract
The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.
This paper presents a comprehensive and updated overview of inborn errors of immunity (IEIs), focusing on the optimal treatment strategies. IEIs or primary immunodeficiencies (PIDs) are a heterogeneous group of approximately 500 disorders, classified into ten categories according to the affected component of the immune system. The clinical presentation varies, based on the type of the disorder and the patient's age.
Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy Tumor Reactive T cell (TRT) Process has been developed.
This study explores a novel therapeutic strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL) by integrating autologous hematopoietic stem cell transplantation (ASCT) with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T cell therapy. A 20-year-old Asian male with refractory BL, whose lymphoma had not responded to multiple chemoimmunotherapy regimens, received myeloablative ASCT followed three days later by infusion of a novel third-generation CAR T cells engineered with CD28 and CD3ζ signaling domains, along with a TLR2 costimulatory domain. This resulted in sustained complete remission at the 306-day follow-up, without experiencing any severe complications.
Senescence occurs earlier in the immune system than in solid organs as age increases. Regulatory T (Treg) cells are among the first cells to exhibit signs of aging. However, whether advanced-age pregnancy involves Treg cell aging remains unclear.
Disease burden is a critical determinant of outcomes in CAR-T therapy for B-cell lymphomas, and one of the most widely used techniques for its assessment is Total Metabolic Tumor Volume (TMTV) measured via [F]FDG PET/CT. Biological parameters may further refine the risk profile. We analyzed baseline [F]FDG PET/CT scans from 40 patients treated with CAR-T, using an AI-based automated segmentation algorithm to determine TMTV.
