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Immunology and Microbiology · Research topic

Open research questions in Immune Cell Function and Interaction

169 unresolved questions extracted from the limitations and future-work sections of 423 Immune Cell Function and Interaction papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Extending the study to other systems of similar receptor organization, - Investigating the dose-response relationships in other antibody-target interactions, - Further studies on the pharmacokinetics and pharmacodynamics of bivalent antibodies

    Modeling effective doses of therapeutic antibodies targeting clustered surface receptors · 2026 · DOI

  • The lack of understanding of the complex biology of bivalent antibodies. The limitations of the traditional dose-finding approach. The need for a mechanistic framework to understand dose-response relationships.

    Modeling effective doses of therapeutic antibodies targeting clustered surface receptors · 2026 · DOI

  • further studies are needed to establish causality between the CCL4-enriched NK-cell transcriptional state and SPP1-positive macrophage and stromal programs, - larger sample sizes are needed to confirm the findings, - studies using single-cell RNA sequencing and spatial transcriptomics can provide further insights into the cellular composition of NK-cell remodeling in CRLM

    A CCL4-enriched NK-cell transcriptional state is associated with inflammatory and myeloid-stromal programs in colorectal cancer liver metastasis · 2026 · DOI

  • The role of NK cells in CRLM is not well understood, particularly their adaptations to the metastatic niche. Prior work has focused on cytotoxic loss and exhaustion-like dysfunction of tumor-infiltrating NK cells, but the underlying mechanisms are not fully characterized. There is a need to integrate multiple datasets and analytical methods to characterize immune and stromal remodeling in CRLM.

    A CCL4-enriched NK-cell transcriptional state is associated with inflammatory and myeloid-stromal programs in colorectal cancer liver metastasis · 2026 · DOI

  • The complexity of the tumor microenvironment and its impact on immune responses. The need to understand the mechanisms by which bacterial RNA affects MHC-I expression and NK cell response. The challenge of translating in vitro findings to in vivo models and clinical applications.

    Bacterial RNA downregulates MHC-I in tumor cell lines, promoting NK response and delaying tumor growth · 2026 · DOI

  • The lack of understanding of the mechanisms by which bacterial RNA affects MHC-I expression and NK cell response in solid tumors. The need for novel therapeutic strategies to promote anti-tumor responses.

    Bacterial RNA downregulates MHC-I in tumor cell lines, promoting NK response and delaying tumor growth · 2026 · DOI

  • understanding the effects of hypoxia on B cell subsets, - investigating the role of IL35 in regulating compensatory immunosuppressive mechanisms, - exploring the potential of targeting CD39 and CD73 ectonucleotidases for cancer therapy

    Dynamic regulation of hypoxia-associated regulatory CD39+CD73+ and IL35+ B cells in pancreatic cancer · 2026 · DOI

  • The effects of hypoxia on B cell subsets in pancreatic cancer are not well understood. The mechanisms by which hypoxia regulates B cell function in the tumor microenvironment are not clearly defined.

    Dynamic regulation of hypoxia-associated regulatory CD39+CD73+ and IL35+ B cells in pancreatic cancer · 2026 · DOI

  • The skin is a highly vascularized tissue, making it challenging to distinguish between circulating and resident NK cells. The experimental design requires careful consideration of the timing and location of NK cell activation. The use of RAG -/- and RAG -/- CD160 -/- mice requires careful interpretation of the results to account for the lack of adaptive immunity.

    CD160 mediated NK cell activation shapes host defense against acute Trypanosoma cruzi infection in the skin · 2026 · DOI

  • Investigate the mechanisms governing early immune activation within barrier tissues, - Examine the role of stromal and epithelial cells in shaping local immunity, - Study the HVEM-CD160 axis in other tissues and immune responses

    CD160 mediated NK cell activation shapes host defense against acute Trypanosoma cruzi infection in the skin · 2026 · DOI

  • Further studies are needed to explore the immunological impact of sex hormones in the specific period of puberty, - Research on the effects of gender-affirming hormone therapy on the immune system is necessary, - Investigations into the mechanisms by which sex hormones modulate the immune response could provide valuable insights, - Studies examining the relationship between sex hormones and immune function in different populations, such as transgender individuals, may be beneficial

    Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy · 2025 · DOI

  • Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood.

    Gut archaea drive human MAIT cell responses · 2026 · DOI

  • Whether and how clonal selection occurs in innate lymphocytes that lack rearranged antigen receptors remains poorly understood.

    Clonal selection of somatic mutations shapes NK cell memory · 2026 · DOI

  • By utilizing a primary human cell model that resembles in vivo conditions across diverse viral strains, we identified that simply preventing CD16 receptor shedding from natural killer (NK) cells is insufficient to improve HIV-1 clearance.

    Fc-engineered broadly neutralizing antibodies overcome cytokine-induced CD16 cleavage to drive potent ADCC against diverse HIV-1 strains · 2026 · DOI

  • However, it remains unclear whether NK cells preferentially take up a specific fatty acid.

    Linoleic Acid Enhances Murine Natural Killer Cell Function In Vitro but Compromises Mitochondrial Bioenergetic Function During Retroviral Infection · 2026 · DOI

  • While CD8+ T cells are largely excluded from GCs, the role of natural killer (NK) cells, potential alternative effectors, remains poorly defined in human LNs during HIV infection.

    Spatial Constraints Limit Natural Killer Cell Access to Germinal Centre HIV Reservoirs in Lymph Nodes · 2026 · DOI

  • Natural killer (NK) cells are critical for early antiviral immunity, yet their metabolic regulation during acute human viral infection remains incompletely understood.

    Single-cell analysis identifies CPT1a-associated metabolic remodeling in human NK cells during COVID-19 · 2026 · DOI

  • However, the fundamental mechanisms that regulate acute infiltration of immune cells from vascular compartments into the CNS are not well defined.

    Myeloid cell IL-15 production in the brain supports bystander CD8+ T cell neuropathic immune responses following virus infection · 2026 · DOI

  • However, the mechanisms that link virus infection in the olfactory neurons and brain injury are not understood.

    Myeloid cell IL-15 production in the brain supports bystander CD8+ T cell neuropathic immune responses following virus infection · 2026 · DOI

  • Preselection DP thymocytes were thought to be relatively homogeneous and TCR modulation during this stage had not been previously described.

    Preselection CD4+CD8+ thymocytes modulate TCR responsiveness following TCRβ selection · 2026 · DOI

  • Future research should focus on integrating mechanistic insights with clinical trial design to optimize NK cell-based therapies for HPV-associated malignancies.

    NK cells in HPV-related tumorigenesis: mechanisms and clinical applications · 2026 · DOI

  • As a member of the proton-sensing GPCR receptors, GPR132 plays a crucial role in regulating immune cell functions, but the mechanism by which GPR132 affects natural killer (NK) cells has not yet been reported.

    GPR132 regulates the function of NK cells through the Gαs/CSK/ZAP70/NF-κB signaling pathway as a potential immune checkpoint · 2025 · DOI

  • In the tumor microenvironment (TME), regulatory T cells (T regs ) adapt their metabolism to thrive in low-glucose, high-lactate conditions, but the mechanisms remain unclear.

    CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor · 2025 · DOI

  • Although several mechanisms have been identified that facilitate immune evasion, the transcriptional programs that orchestrate this process remain poorly understood.

    ZNF296 Drives Immune Evasion in Epithelial Cancers by Repressing Immune Stimulatory Genes · 2025 · DOI

  • While the immunological mechanisms remain unclear, enhanced nitric oxide production by immune effector cells may play a role in this association.

    Interplay of KIR2DL5, nitric oxide, and tobacco smoking in predisposition to bladder cancer · 2025 · DOI

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169 open questions have been extracted from the limitations and future-work passages of 423 Immune Cell Function and Interaction 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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