Trends in Immunology最新文献

Natural killer (NK) cells protect from viral infection, cancer, and metastasis, and are emerging as valuable therapeutics for cancer treatment. NK-cell control of viral infection has been studied intensively, but less is known in the context of cancer. Multiple associative, preclinical, and early phase clinical studies have revealed the ability of NK-cell-based therapies to contribute to cancer control. Development of effective NK-cell therapeutics will be facilitated by a deeper understanding of the mechanisms controlling NK cell function across an array of cancer types and states. This review will focus on recent studies of the transcription factors that control NK cell function and their response to leukemia, solid tumors, and metastasis.

Burn et al. reveal a previously unrecognised, non-catalytic function of myeloperoxidase (MPO) in neutrophil extracellular trap (NET) formation; integrating super-resolution microscopy and biochemical approaches, they demonstrated that MPO's oligomeric state governs chromatin decondensation, redefining MPO as a structural chromatin modifier with implications for diseases driven by dysregulated NETosis.

Sepsis, a life-threatening condition triggered by infection, disrupts the body's immune balance and remains a major global health challenge. This forum explores the dual roles of cytokines in sepsis: their overactivation drives 'cytokine storms,' and dysregulation leads to immunosuppression. It also discusses regulatory mechanisms for developing targeted therapies.

This essay uses immunology to illuminate human relationships. Moving beyond self/non-self toward danger-based models, it draws parallels between cytokine communication and language, tolerance and forgiveness, microbiota diversity and coexistence. Recognizing these metaphors reveals pathways toward healthier connections within individuals, communities, and societies.

HIV-1 persists lifelong despite effective antiretroviral therapy, yet the mechanisms underlying this persistence remain incompletely understood. Recent work by Wei et al. and Gao et al. reveals that the transcription factor BACH2 orchestrates CD4⁺ T cell memory programs fostering long-term memory formation while limiting effector differentiation, thereby promoting HIV-1 persistence.

Mitochondrial lipid metabolism plays a pivotal role in tumor immunosurveillance and immune evasion. This review explores how mitochondrial regulation shapes immune cell metabolism within the tumor microenvironment (TME), focusing on the antitumor effects of the mitochondrial-fueled immune response and the detrimental impact of impaired mitochondrial function on immune cell cytotoxicity. Although current studies support this dual role, critical gaps remain, including how immune cells adapt differently to the lipid-rich TME, and how therapies can target lipid metabolism without harming immune memory. By synthesizing current findings and highlighting these uncertainties, this review highlights mitochondrial lipid metabolism as a promising therapeutic axis in cancer immunotherapy.

The interaction between the tumor immune microenvironment (TIME) and the tumor determines whether immune evasion or antitumor immunity prevails. Metabolic reprogramming is increasingly recognized as a critical factor shaping the tumor immune response. Glucose metabolism regulates the intrinsic cellular states of both immune and tumor cells, while simultaneously shaping the surrounding microenvironment. The glycolytic diversity of immune and tumor cells drives the complexity of the TIME. In this Review, we explore how glucose metabolism remodels the TIME and how these metabolic alterations influence immune effector function and immune evasion. We also highlight the potential for integrating microenvironmental modulation as a promising therapeutic strategy in glucose-targeted cancer therapies.

Programmed cell death (PCD) encompasses several tightly regulated molecular signalling pathways, leading to the controlled destruction of cells. Apoptosis is a non-immunogenic form of cell death that regulates homeostasis to cell stressors. In contrast, lytic forms of cell death - necroptosis, pyroptosis, and ferroptosis - promote inflammation, alerting the immune system to danger. As adaptive immune responders, T cells clonally expand in response to antigenic stimulation and rapidly contract following the clearance of infection. While the role of apoptosis in regulating these processes is relatively well understood, evidence for lytic death activity in T cells is emerging. This review provides an update on recent advances in the understanding of PCD pathways in conventional and unconventional T cells in diverse immune contexts.

The maintenance of serum antibodies requires the persistence of plasma cells within the bone marrow (BM). However, little is understood about why relatively few BM plasma cells live for extended periods. We consider two opposing viewpoints. We first consider the notion that sustained antibody titers requires localization of plasma cells to specialized BM niches where they access cell extrinsic survival factors, including extracellular ATP (eATP). We then consider the alternative possibility that plasma cell survival requires optimized cell intrinsic control of antibody synthesis supported by eATP stimulation of purinergic receptors. Based on the latter view we propose that many BM plasma cells fail to achieve maximal longevity due to suboptimal protein homeostasis rather than compromised access to cell extrinsic survival cues.

Interleukin-27 (IL-27), a member of the IL-12 cytokine family, was long viewed primarily as a regulator of CD4⁺ T cell immunity. Subsequent studies revealed that IL-27 also directly modulates CD8⁺ T cells, displaying both stimulatory and inhibitory potential. Recent work extends this earlier literature, showing that IL-27 in infection and cancer can promote effector differentiation, sustain survival, and reverse dysfunction, often without the systemic toxicity associated with related cytokines. This review outlines the molecular features, signaling mechanisms, and cellular sources of IL-27, integrating emerging evidence from viral, tumor, and autoimmune settings. We propose that IL-27 operates not as an inherently pro- or anti-inflammatory cytokine but as a context-dependent tuner of CD8⁺ T cell cytotoxic immunity, offering new opportunities for therapeutic exploitation.