Trends in Immunology

Trends Immunol. 2025 Jun 18:S1471-4906(25)00143-7. doi: 10.1016/j.it.2025.06.002. Online ahead of print. ABSTRACT Two recent studies, by Ely et al. and Apavaloaei et al., revealed that non-canonical antigens derived from unmutated, noncoding regions dominate the immunopeptidome of many cancers. Here, we discuss how this challenges conventional mutation-centric immunotherapies and highlight emerging strategies, including cryptic antigen- and … Read more

Trends Immunol. 2025 Jun 16:S1471-4906(25)00140-1. doi: 10.1016/j.it.2025.05.005. Online ahead of print. ABSTRACT Exploiting specific T cell subset properties bears potential for T cell therapies but is complicated by inconsistencies in T cell subset definitions and markers. Here, we discuss causes for the definition and classification complexities to provide a handle for how to navigate the … Read more

Trends Immunol. 2025 Jun 14:S1471-4906(25)00125-5. doi: 10.1016/j.it.2025.05.004. Online ahead of print. ABSTRACT Multiomics advances have led to breakthroughs in understanding human early life immunity. Adaptive memory immune cells have been detected in fetal tissue extremely early in gestation, where they may respond to maternal exposures. These promising findings lay the groundwork for future research on … Read more

Trends Immunol. 2025 Jun 11:S1471-4906(25)00124-3. doi: 10.1016/j.it.2025.05.003. Online ahead of print. ABSTRACT Organisms must adapt to unpredictable environmental perturbations. We propose that the immune system, which can be redistributed across tissues (‘immune innervation’), cooperates with the nervous system to form a larger integrative network that can maximize the number of adaptive physiologic states to a … Read more

Trends Immunol. 2025 May 27:S1471-4906(25)00121-8. doi: 10.1016/j.it.2025.04.008. Online ahead of print. ABSTRACT Active regulation of T cell quiescence is important to sustain immune responses to vaccination and infection while preventing inappropriate responses such as autoimmunity. Recent studies highlight that quiescence in naïve T cells is actively regulated by transcription factors and tonic signaling. Loss of … Read more

Trends Immunol. 2025 May 26:S1471-4906(25)00123-1. doi: 10.1016/j.it.2025.05.002. Online ahead of print. ABSTRACT Understanding the mechanisms implicated in the establishment of trained immunity could aid the design of novel therapeutic approaches. By studying Bacille Calmette-Guerin (BCG) vaccination in a human cohort, Ziogas and colleagues demonstrate the role of lactate generation and its use for histone lactylation … Read more

Trends Immunol. 2025 May 26:S1471-4906(25)00122-X. doi: 10.1016/j.it.2025.05.001. Online ahead of print. ABSTRACT Microglia replacement is reshaping neurodegenerative disease therapy, yet its key prerequisites remain unclear. In the current issue of Immunity, Aisenberg et al. and Bastos et al. reveal how developmental origin influences monocyte engraftment into the brain, and demonstrate the therapeutic potential of monocyte-based … Read more

Trends Immunol. 2025 May 20:S1471-4906(25)00095-X. doi: 10.1016/j.it.2025.04.003. Online ahead of print. ABSTRACT N6-methyladenosine (m6A) is a key mRNA modification influencing mRNA stability and translation. YTHDF2, a major m6A ‘reader’, was initially recognized for promoting mRNA decay but is now also known to enhance translation by binding to methylated mRNAs. YTHDF2 maintains the function of immune … Read more

Trends Immunol. 2025 May 19:S1471-4906(25)00116-4. doi: 10.1016/j.it.2025.04.005. Online ahead of print. ABSTRACT Proteins with a Toll/interleukin-1 receptor/resistance (TIR) domain are among the most ancient immune regulators and include well-known pattern recognition receptors (PRRs). A specialized subset of TIR domain proteins are enzymes that predominantly use nicotinamide adenine dinucleotide (NAD+) to generate second messenger metabolites. These … Read more

Trends Immunol. 2025 May 16:S1471-4906(25)00119-X. doi: 10.1016/j.it.2025.04.006. Online ahead of print. ABSTRACT Although DNA damage is a common cellular event, T cells experience significant genotoxic stresses because of rapid antigen-stimulated expansion and their presence in various nonlymphoid microenvironments. In addition to the well-established link between genomic instability and malignancy, recent genomic studies have uncovered a … Read more