Articles (6)

Review

31 March 2025

Advances in CAR-T Cell Therapy for Solid Tumors

Chimeric Antigen Receptor T (CAR-T) cell therapy represents a groundbreaking advancement in cancer treatment, demonstrating remarkable antitumor efficacy in hematological malignancies. However, despite the substantial clinical progress achieved with CAR-T cell therapy, its application in the treatment of solid tumors remains limited by various factors, including the intricate tumor microenvironment (TME), CAR-T cell exhaustion, CAR-T cell infiltration into tumor tissue, and antigen heterogeneity. Scientists are relentlessly pursuing research in this domain, driven by the aim of offering newfound hope to cancer patients. In this comprehensive review, we delineate the fundamental principles underlying CAR-T cell therapy, delve into the challenges it encounters, and provide an insightful exploration of the advancements and progress made in the application of CAR-T cell therapy for solid tumors.

Yitong  Li
Baile  Zuo
Yating Xing
Rui  Zhang
Lintao  Jia
Bo  Yan
Angang  Yang*
Huilong  Yin*

Review

21 March 2025

Metabolic Regulation of T Cell Exhaustion

Cytotoxic CD8 T cells play a crucial role in controlling tumor progression. However, T cells infiltrating tumor tissues upregulate inhibitory receptors, reduce cytokine secretion, and lose their killing function, a state known as exhaustion. Thus, preventing or reversing T cell exhaustion is essential for sustaining a successful antitumor immune response. Recent studies have shown that T cell immunity not only requires the three primary signals—antigen receptor signaling, costimulation, and cytokines—but is largely shaped by endogenous and ambient metabolites as a fourth regulatory signal. Therefore, metabolic changes in the tumor microenvironment, caused by tumor cell proliferation and tissue remodeling, have a significant impact on the function of tumor-infiltrating T cells. This paper will review mechanisms by which three major types of metabolites—carbohydrates, lipids, and amino acids—influence T cell exhaustion in the tumor microenvironment, providing insights and directions for exploring metabolic targets in antitumor immunity.

Hao Wu*
Miriam Campillo  Prados
Martin Vaeth

Opinion

21 March 2025

Classical MHC Class I Molecules as Modifiers of Brain Homeostasis and Neuroregeneration: Unraveling the Riddle?

As mankind breaks the boundaries of potential years to live, the process of aging imposes various cellular challenges, from less capacity of cell repair and damage to impaired protein formation, causing chronic low-level inflammation on tissues including the brain. Persistent chronic neuroinflammation can harm neurons, contributing to the development of neurodegeneration, a pathological process that affects cognitive function and is often reflected by dementia. This opinion article tries to recapitulate the influence that major histocompatibility class I (MHC-I) molecules have on brain homeostasis and how abnormalities in their expression can lead to cognitive deterioration. Studies carried out during recent years not only demonstrated that neurons and other central nervous system (CNS) cells express MHC-I molecules, but also that these molecules play essential roles in the establishment, function, and modeling of synapses in the CNS during the embryonic period, at birth and during adulthood, namely during inflammatory conditions. The accumulated body of evidence suggests that MHC-I molecules and the signaling pathways they regulate could provide clues on some of the molecular and cellular mechanisms regulating brain homeostasis and neuroregeneration in health and disease, thus becoming potential biomarkers of cognitive decline and targets for innovative immunotherapies.

Fernando A.Arosa*
Elsa M.Cardoso
Ricardo  A. S.Carvalho

Article

14 January 2025

CYLD Regulates T Cell Metabolism and Mitochondrial Autophagy through LKB1/AMPKα Pathway

The deubiquitinating enzyme cylindromatosis (CYLD) plays a fundamental role in regulating T cell development and activation. Previous studies have shown that CYLD is associated with autophagy, while AMP activated protein kinase (AMPK) pathway regulates the development of autophagy and affects cell metabolism. However, the mechanism by which CYLD affects autophagy and whether it affects the downstream metabolism of AMPKα remains unclear. In this study, we used the CYLD gene knockout model in Jurkat cells to investigate the mechanism of CYLD and autophagy and its relationship with cellular metabolism. The results show that CYLD deletion promotes autophagy through AMPKα/mTOR/ULK1 signaling pathway, promotes mitochondrial autophagy to improve mitochondrial function and attenuates cell lipid metabolism in Jurkat cells.

Lu Yu
Ge Gao
Jingtao Gao
Yuxin Zhao
Yuna Niu
Jianping Ye
Yinming Liang
Hui  Wang*

Review

02 January 2025

Cell-Autonomous and Non-Cell-Autonomous Antiviral Immunity via siRNA-Directed RNAi in Drosophila melanogaster

In Drosophila melanogaster, the siRNA-directed RNAi pathway provides crucial antiviral defenses. Cell-autonomously, Dicer-2 (Dcr-2) recognizes and cleaves viral dsRNA into siRNAs, which are incorporated into the RNA-induced silencing complex (RISC). Argonaute 2 (Ago2) then targets and cleaves viral RNA, preventing replication. Non-cell-autonomously, infected hemocytes secrete exosomes containing viral siRNAs, spreading antiviral signals to other cells. Additionally, tunneling nanotubes can transfer RNAi components between neighboring cells, further enhancing systemic immunity. These findings highlight the sophisticated antiviral strategies in Drosophila, offering insights for broader antiviral research.

Haojiang  Luan*

Editorial

04 June 2024
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