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1.
Int J Mol Sci ; 23(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35270020

RESUMO

Along with the clinical success of immuno-oncology drugs and cellular therapies, T-cell biology has attracted considerable attention in the immunology community. Long-term immunity, traditionally analyzed in the context of infection, is increasingly studied in cancer. Many signaling pathways, transcription factors, and metabolic regulators have been shown to participate in the formation of memory T cells. There is increasing evidence that the signal transducer and activator of transcription-3 (STAT3) signaling pathway is crucial for the formation of long-term T-cell immunity capable of efficient recall responses. In this review, we summarize what is currently known about STAT3 role in the context of memory T-cell formation and antitumor immunity.


Assuntos
Células T de Memória , Neoplasias , Humanos , Neoplasias/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
2.
Front Immunol ; 15: 1301378, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495874

RESUMO

Asymmetric cell division is a fundamental process conserved throughout evolution, employed by both prokaryotic and eukaryotic organisms. Its significance lies in its ability to govern cell fate and facilitate the generation of diverse cell types. Therefore, attaining a detailed mechanistic understanding of asymmetric cell division becomes essential for unraveling the complexities of cell fate determination in both healthy and pathological conditions. However, the role of asymmetric division in T-cell biology has only recently been unveiled. Here, we provide an overview of the T-cell asymmetric division field with the particular emphasis on experimental methods and models with the aim to guide the researchers in the selection of appropriate in vitro/in vivo models to study asymmetric division in T cells. We present a comprehensive investigation into the mechanisms governing the asymmetric division in various T-cell subsets underscoring the importance of the asymmetry in fate-determining factor segregation and transcriptional and epigenetic regulation. Furthermore, the intricate interplay of T-cell receptor signaling and the asymmetric division geometry are explored, shedding light on the spatial organization and the impact on cellular fate.


Assuntos
Divisão Celular Assimétrica , Epigênese Genética , Diferenciação Celular , Subpopulações de Linfócitos T , Imunoterapia
3.
Front Immunol ; 13: 971045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268015

RESUMO

FOXP1 is ubiquitously expressed in the human body and is implicated in both physiological and pathological processes including cancer. However, despite its importance the role of FOXP1 in T-cells has not been extensively studied. Although relatively few phenotypic and mechanistic details are available, FOXP1 role in T-cell quiescence and differentiation of CD4+ subsets has recently been established. FOXP1 prevents spontaneous T-cell activation, preserves memory potential, and regulates the development of follicular helper and regulatory T-cells. Moreover, there is growing evidence that FOXP1 also regulates T-cell exhaustion. Altogether this makes FOXP1 a crucial and highly undervalued regulator of T-cell homeostasis. In this review, we discuss the biology of FOXP1 with a focus on discoveries made in T-cells in recent years.


Assuntos
Fatores de Transcrição Forkhead , Proteínas Repressoras , Humanos , Fatores de Transcrição Forkhead/genética , Diferenciação Celular , Ativação Linfocitária , Linfócitos T Reguladores
4.
Cancers (Basel) ; 14(4)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35205827

RESUMO

Immunotherapy using chimeric antigen receptor (CAR) T cells is a promising option for cancer treatment. However, T cells and CAR-T cells frequently become dysfunctional in cancer, where numerous evasion mechanisms impair antitumor immunity. Cancer frequently exploits intrinsic T cell dysfunction mechanisms that evolved for the purpose of defending against autoimmunity. T cell exhaustion is the most studied type of T cell dysfunction. It is characterized by impaired proliferation and cytokine secretion and is often misdefined solely by the expression of the inhibitory receptors. Another type of dysfunction is T cell senescence, which occurs when T cells permanently arrest their cell cycle and proliferation while retaining cytotoxic capability. The first section of this review provides a broad overview of T cell dysfunctional states, including exhaustion and senescence; the second section is focused on the impact of T cell dysfunction on the CAR-T therapeutic potential. Finally, we discuss the recent efforts to mitigate CAR-T cell exhaustion, with an emphasis on epigenetic and transcriptional modulation.

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