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Immunology and Microbiology · Research topic

Open research questions in interferon and immune responses

152 unresolved questions extracted from the limitations and future-work sections of 346 interferon and immune responses papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The study used public multi-omics datasets and two single-cell RNA-sequencing cohorts, - The study had a limited number of clinical tissue samples, - The study did not investigate the underlying mechanisms of ISG20L2 in gastric cancer

    Multi-omics and experimental validation reveal ISG20L2 as a potential pro-oncogenic regulator in gastric cancer · 2026 · DOI

  • Investigate the underlying mechanisms of ISG20L2 in gastric cancer, - Explore the potential of ISG20L2 as a therapeutic target for gastric cancer, - Examine the association between ISG20L2 expression and clinical outcomes in gastric cancer patients

    Multi-omics and experimental validation reveal ISG20L2 as a potential pro-oncogenic regulator in gastric cancer · 2026 · DOI

  • Available evidence is largely case-based, - Does not establish population prevalence or a causal relationship between LHON mutations and MS, - Limited human evidence

    Sterile inflammation in LHON: mitochondrial stress, innate immune signaling, and implications for AAV gene therapy · 2026 · DOI

  • The traditional pathogenic model of LHON does not fully explain the disease's variability. The role of immune signaling in LHON is not well understood. The relationship between mitochondrial dysfunction and sterile inflammatory responses in LHON is not fully elucidated.

    Sterile inflammation in LHON: mitochondrial stress, innate immune signaling, and implications for AAV gene therapy · 2026 · DOI

  • validation in independent populations is needed, - the study has limitations due to the complex pathophysiological mechanisms of the disease, - the existing early diagnostic method has limitations

    The cGAS-STING pathway in acute myocardial infarction: Biomarker discovery and mechanistic insights · 2026 · DOI

  • validation of the findings in independent populations, - further analysis of the cGAS-STING pathway in AMI, - investigation of the potential of PFKFB3 and TLR2 as diagnostic biomarkers

    The cGAS-STING pathway in acute myocardial infarction: Biomarker discovery and mechanistic insights · 2026 · DOI

  • Controlled, tumor-localized, and time-limited STING activation - Systemic administration limitations for many STING agonists - Distinguishing between therapeutic opportunity and compensatory resistance

    STING-mediated tumor microenvironment remodeling: turning adaptive resistance into therapeutic vulnerability · 2026 · DOI

  • First-generation cyclic dinucleotide agonists may be limited by rapid clearance, poor membrane permeability, inefficient cytosolic delivery, and insufficient tumor accumulation. Systemic administration remains challenging for many STING agonists due to potential inflammatory toxicity. The strategy proposed here depends on controlled, tumor-localized, and time-limited STING activation rather than generalized innate immune stimulation.

    STING-mediated tumor microenvironment remodeling: turning adaptive resistance into therapeutic vulnerability · 2026 · DOI

  • The full mapping of PTM landscape of ZBP1 and IFI16 remains a top priority in the field requiring quantitative mass spectrometry across different infection models, - The consequences of SUMOylation of ZBP1 in infection models are not fully characterized yet, - Species-specific differences may still exist between human IFI16 and its murine functional homolog p204

    ZBP1 and IFI16: novel innate sensors and inflammation regulation under infection stress · 2026 · DOI

  • Further studies are needed to fully characterize the consequences of SUMOylation of ZBP1 in infection models, - The full mapping of PTM landscape of ZBP1 and IFI16 is required, - Investigating the therapeutic potential of targeting ZBP1 and IFI16 in autoimmune diseases and viral infections

    ZBP1 and IFI16: novel innate sensors and inflammation regulation under infection stress · 2026 · DOI

  • Background: Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier induced by inflammatory cues, yet its functional relevance in cancer remains unclear and context dependent.

    Integrative pan-cancer analysis suggests ISG15-linked immune and phosphoproteomic divergence between KIRC and KICH · 2026 · DOI

  • How host and viral factors rewire the mitochondrial proteome during infection to shape these outcomes remains incompletely understood.

    The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection · 2026 · DOI

  • Although macrophages are known to contribute to inflammation through glycolytic bursts that support rapid energy production, the role of the stimulator of interferon genes (STING) in orchestrating macrophage glycolysis and modulating phenotypic polarization remains poorly defined.

    STING controls glycolysis and histone lactylation to drive macrophage metabolic reprogramming in postoperative ileus · 2026 · DOI

  • tb infection, but the mechanisms controlling their induction remain incompletely defined.

    Mycobacterium tuberculosis Rv3248c Inhibits Type I Interferon Response and Promotes Intracellular Survival by Mediating Ubiquitin-Proteasome-Dependent Degradation of TBK1 · 2026 · DOI

  • The potential of vaccine adjuvants to facilitate such cross-organ induction of mucosal immunity, given their established role in enhancing and shaping immune responses, is currently not well understood.

    Adjuvants orchestrate cross-organ induction of mucosal CD8+ T cell immune responses in respiratory tracts · 2026 · DOI

  • While the flavonoid rutin exhibits documented anti-inflammatory and antioxidant properties, its therapeutic mechanisms in ALI/ARDS remain unclear.

    Rutin ameliorates LPS-induced acute lung injury in mice by inhibiting the cGAS-STING-NLRP3 signaling pathway · 2025 · DOI

  • The mechanisms and functions of STING-induced autophagy remain poorly understood.

    STING-induced noncanonical autophagy regulates endolysosomal homeostasis · 2025 · DOI

  • However, the molecular mechanisms whereby cytosolic DNA-induced cGAS-STING pathway leads to aging remain poorly understood.

    A noncanonical cGAS–STING pathway drives cellular and organismal aging · 2025 · DOI

  • Dysregulated stimulator of interferon genes (STING) signaling is implicated in neurodegenerative disorders, yet the biological interaction between this pathway and Aβ, as well as their combined influence on AD progression, is poorly understood.

    Nanoimmunomodulation of the Aβ-STING feedback machinery in microglia for Alzheimer’s disease treatment · 2025 · DOI

  • While several monoclonal antibodies targeting Aβ have shown reductions in amyloid burden, their impact on cognitive function remains controversial, with the added risk of inflammatory side effects.

    Nanoimmunomodulation of the Aβ-STING feedback machinery in microglia for Alzheimer’s disease treatment · 2025 · DOI

  • While the mechanisms by which SARS-CoV-2 evades host recognition of its RNA are well studied, how it evades immune responses to cytosolic DNA-leaked from mitochondria or nuclei during infection-remains poorly understood.

    SARS-CoV-2 nucleocapsid protein directly prevents cGAS–DNA recognition through competitive binding · 2025 · DOI

  • Besides topoisomerase toxicity, Doxorubicin is also toxic to the mitochondria yet the underlying late onset mechanism remains elusive.

    Mitochondrial Amount Determines Doxorubicin‐Induced Cardiotoxicity in Cardiomyocytes · 2025 · DOI

  • However, the precise mechanisms through which cGAS activation influences AD progression remain poorly understood.

    Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid‐β‐Induced Pathogenesis of Alzheimer's Disease · 2025 · DOI

  • However, the regulation of AGOs and how their functions adapt to genetic or environmental perturbations remains incompletely understood.

    Dynamic control of Argonautes by a rapidly evolving immunological switch · 2025 · DOI

  • Luteolin, a flavonoid commonly found in traditional herbs, shows potential as an anti-ALI agent in pharmacological and clinical research, although its biological mechanism is not fully understood.

    Luteolin Mitigates Acute Lung Injury Through Immune Modulation and Antinecroptosis Effects by Targeting the BTK and FLT3 Signaling Pathways · 2025 · DOI

Most-cited papers in interferon and immune responses

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152 open questions have been extracted from the limitations and future-work passages of 346 interferon and immune responses papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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