Clinical Immunology, Год журнала: 2025, Номер 275, С. 110486 - 110486
Опубликована: Март 20, 2025
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Май 13, 2023
Abstract Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend develop a characteristic inflammatory state expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is typical phenomenon immunosenescence it considered the major risk factor for diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, epigenetic alterations striking features immunosenescence. Disturbed T-cell pools antigen stimulation mediate premature senescence cells, senescent cells proinflammatory senescence-associated secretory phenotype exacerbates Although underlying molecular mechanisms remain be addressed, well documented T inflammaging might driving forces in Potential counteractive measures will discussed, including intervention cellular metabolic-epigenetic axes mitigate In recent years, has attracted increasing attention its role tumor development. As result limited participation elderly patients, impact on cancer immunotherapy unclear. Despite some surprising results from clinical trials drugs, necessary investigate other
Язык: Английский
Процитировано
314
Nature Metabolism, Год журнала: 2023, Номер 5(2), С. 314 - 330
Опубликована: Янв. 30, 2023
The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions tumor-infiltrating lymphocytes (TILs). However, it remains unclear how an environment affects T cell metabolism and differentiation. Here we show that prolonged exposure to acid reprograms intracellular mitochondrial fitness preserves stemness. Mechanistically, elevated extracellular acidosis impairs methionine uptake via downregulation SLC7A5, therefore altering H3K27me3 deposition at promoters key stemness genes. These changes promote maintenance a 'stem-like memory' state improve long-term in vivo persistence anti-tumor efficacy mice. Our findings not only reveal unexpected capacity maintain stem-like properties cells, but also advance our understanding
Язык: Английский
Процитировано
68
Cell, Год журнала: 2023, Номер 186(8), С. 1541 - 1563
Опубликована: Апрель 1, 2023
Язык: Английский
Процитировано
62
Trends in Immunology, Год журнала: 2023, Номер 44(3), С. 231 - 244
Опубликована: Фев. 9, 2023
T cell subsets adapt and rewire their metabolism according to functions surrounding microenvironment. Whereas naive cells rely on mitochondrial metabolic pathways characterized by low nutrient requirements, effector induce kinetically faster generate the biomass energy needed for proliferation cytokine production. Recent findings support concept that alterations in also affect epigenetics of cells. In this review we discuss connections between epigenetic changes such as histone post-translational modifications (PTMs) DNA methylation, well 'extra-metabolic' roles enzymes molecules. These collectively point a new group potential therapeutic targets treatment cell-dependent autoimmune diseases cancers.
Язык: Английский
Процитировано
44
Clinical Immunology, Год журнала: 2023, Номер 249, С. 109289 - 109289
Опубликована: Март 12, 2023
Язык: Английский
Процитировано
41
Molecular Cell, Год журнала: 2024, Номер 84(4), С. 760 - 775.e7
Опубликована: Янв. 11, 2024
Язык: Английский
Процитировано
31
Nature Immunology, Год журнала: 2024, Номер 25(6), С. 1033 - 1045
Опубликована: Май 14, 2024
Язык: Английский
Процитировано
21
Cell Metabolism, Год журнала: 2022, Номер 35(1), С. 36 - 55
Опубликована: Дек. 5, 2022
Язык: Английский
Процитировано
67
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12317 - 12317
Опубликована: Авг. 1, 2023
As an emerging treatment strategy for malignant tumors, chimeric antigen receptor T (CAR-T) cell therapy has been widely used in clinical practice, and its efficacy markedly improved the past decade. However, effect of CAR-T is not so satisfying, especially solid tumors. Even hematologic malignancies, a proportion patients eventually relapse after receiving infusions, owing to poor expansion persistence cells. Recently, CRISPR/Cas9 technology provided effective approach promoting proliferation cells body. This utilized generate memory phenotype, reduce exhaustion, screen new targets improve anti-tumor potential. In this review, we aim describe major causes limiting discuss application function. Finally, investigate trials CRISPR/Cas9-engineered cancer.
Язык: Английский
Процитировано
36
Cell Reports Medicine, Год журнала: 2023, Номер 4(3), С. 100978 - 100978
Опубликована: Март 1, 2023
Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previously reported that transient engineering tumor-specific CD8 cells with IL-12 mRNA enhanced their systemic efficacy when delivered intratumorally. Here, we mix engineered mRNAs to express either single-chain (scIL-12) or an IL-18 decoy-resistant variant (DRIL18) is not functionally hampered by binding protein (IL-18BP). These mRNA-engineered mixtures are repeatedly injected into mouse tumors. Pmel-1 receptor (TCR)-transgenic electroporated scIL-12 DRIL18 exert powerful effects in local and distant melanoma lesions. associated metabolic fitness, miR-155 control on immunosuppressive target genes, expression various cytokines, changes glycosylation profile surface proteins, enabling adhesiveness E-selectin. Efficacy this intratumoral immunotherapeutic strategy recapitulated cultures tumor-infiltrating lymphocytes (TILs) chimeric antigen (CAR) electroporation.
Язык: Английский
Процитировано
33