What Cytokine Profiling & Immunomonitoring got wrong, from 34 theses

Tried and failed

cytokine profiling to predict mortality applied to polymicrobial sepsis disease outcomes. Outcome: no signal. Reason: circulating and lung cytokine levels paradoxically decoupled from and failed to correlate with sex-specific survival differences

The role of gender in susceptibility to infection and sepsis · Imperial · PhD

Tried and failed

baseline biomarker profiling for treatment outcome prediction applied to predicting systemic immunosuppressive therapy outcomes. Outcome: no signal. Reason: baseline serum cytokine/chemokine concentrations lacked practically significant predictive power for treatment outcomes

Towards a data-driven personalised management of Atopic Dermatitis severity · Imperial · PhD

Tried and failed

multiplex cytokine profiling and correlation analysis applied to perioperative systemic inflammation markers. Outcome: no signal. Reason: No significant plasma cytokine correlations survived multiple testing correction across perioperative timepoints.

Brain inflammation following surgery for fractured neck of femur · Imperial · Doctorate

Tried and failed

ELISA profiling of proinflammatory cytokines applied to first-trimester preterm labor prediction. Outcome: no signal. Reason: Cytokine concentrations showed no statistically significant differences between preterm labor and term control cohorts

Early prediction of pregnancy disorders with machine learning guided Raman spectroscopy, and metabolomics. · Iowa State · Master's

Tried and failed

serum cytokine profiling for chronic disease pathology applied to post-viral infection animal models. Outcome: no signal. Reason: pro-inflammatory cytokine levels did not significantly differ between infected and uninfected animals at late timepoints

Pathogenic Models for Studying Broadly Protective Vaccines and Post-Acute Sequelae of COVID-19 (PASC) · Cornell · PhD

Tried and failed

multiplex cytokine immunoassay profiling across surgical timepoints applied to circulating plasma biomarkers during liver regeneration. Outcome: no signal. Reason: no statistically significant differences in circulating cytokine levels between pre-stage 1 and pre-stage 2 timepoints

Mechanisms of liver regeneration in a clinical model for preoperative induction of liver hypertrophy prior to major liver resection · Imperial · PhD

Tried and failed

serum inflammatory biomarker profiling for infection status applied to differentiating viral infection in chronic disease. Outcome: no signal. Reason: Systemic IL-6 and MPO levels did not significantly differ between infected and uninfected baseline cohorts.

RSV associated COPD exacerbation prevalence and severity · Imperial · PhD

Tried and failed

correlating patient-reported symptom severity with circulating inflammatory biomarkers applied to respiratory exacerbation during antibiotic treatment. Outcome: no signal. Reason: symptoms did not track CRP or IL-6 levels during ongoing therapy

An exploration of symptom clusters, symptoms, and blood-based biomarkers in people with cystic fibrosis during an acute pulmonary exacerbation · UT Austin · PhD

Tried and failed

correlating peripheral and central inflammatory biomarker levels applied to post-operative systemic and neuroinflammation monitoring. Outcome: no signal. Reason: blood and CSF cytokine concentrations did not significantly correlate after surgery

Assessment and quantification of cytokine changes following surgery · Imperial · Doctorate

Tried and failed

multiplex immunoassay of local biofluid biomarkers applied to localized inflammatory tissue pathology. Outcome: no signal. Reason: Biomarker concentration differences between diseased and control sites lacked statistical significance.

Effect of endodontic treatment on local inflammatory biomarkers in teeth with apical periodontitis · Harvard · Master's

Tried and failed

measuring synovial fluid cytokine biomarker panels applied to joint injury disease classification. Outcome: no signal. Reason: Cytokine concentrations did not differ significantly between diseased and healthy controls.

LUBRICIN IN POST-TRAUMATIC OSTEOARTHRITIS, FROM NATURALLY OCCURRING DISEASE TO RECOMBINANT THERAPEUTICS · Cornell · PhD

Tried and failed

serum biomarker quantification for disease activity monitoring applied to autoimmune vasculitis disease progression. Outcome: no signal. Reason: circulating biomarker levels showed no correlation with standard clinical inflammatory markers or antibody titres

Factors affecting outcome in ANCA associated vasculitis · Imperial · PhD

Tried and failed

set-level permutation analysis of biomarker correlations applied to plasma cytokines and composite cognitive scores. Outcome: no signal. Reason: no significant association was found across subjects or over time

Validating the Cognitron online cognitive assessment technology for large scale remote citizen science, clinical trials and individual assessment applications · Imperial · PhD

Lost to a baseline

1 conditioned macrophage culture supernatant sample (SHCC92) excluded from MSD cytokine analysis due to undetectable analyte levels across all measured cytokines.

Characterising Mer and Axl receptor tyrosine kinase expression and transcriptomic profiling of myeloid cells in hepatocellular carcinoma · Imperial · PhD

Tried and failed

cytokine multiplex array applied to frozen tissue lysates across biological stages. Outcome: no signal. Reason: insufficient sensitivity or tissue degradation masking expression differences in low-abundance effector molecules

ILC3 dynamics at the human uterine mucosal interface – a focus on IL-22 · Imperial · PhD

Lost to a baseline

Synovial fluid samples with dilution factors greater than 10 (measured by urea assay) were excluded from cytokine array analysis.

Self-Healing Hyaluronic Acid as a Viscosupplement and Biomolecule Carrier to Mitigate Post-Traumatic Osteoarthritis · Duke · PhD

Considered and rejected

Considered and rejected: Rejected calculating absolute cytokine concentrations from Luminex standard curves because standard-curve values were out of range, opting instead to analyze raw fluorescence intensity levels

Investigating the role of cytokines in clonal hematopoiesis · Oxford · Master's

Considered and rejected

Considered and rejected: Retired sandwich ELISA for IFN-alpha in favor of multiplex ELISA due to poor sensitivity in detecting low cytokine concentrations

Toll-like Receptor 7 modulation of the immune response in seasonal allergic rhinitis · Imperial · PhD

Tried and failed

peripheral immune cell profiling as disease biomarker applied to liver cirrhosis severity staging. Outcome: no signal. Reason: circulating NK receptor expression and degranulation did not correlate with clinical severity scores

Natural Killer cells in cirrhosis and hepatocellular carcinoma and the role of LLT1 in the Liver and in hepatocellular carcinoma · Imperial · PhD

Tried and failed

cytokine receptor profiling as clinical marker applied to antigen-specific cytotoxic T cells. Outcome: no signal. Reason: receptor expression levels showed no correlation with helper T cell counts or percentages

HIV-1 CD8+ T cell emergence, evolution and virus control · Imperial · Doctorate

Tried and failed

baseline target expression as response predictor applied to combination immune checkpoint blockade response. Outcome: no signal. Reason: baseline receptor expression levels did not correlate with pathological treatment response

Biomarkers predicting outcomes for melanoma patients receiving systemic treatment · UT Austin · PhD

Tried and failed

baseline immune repertoire profiling and cell ratios applied to predicting immunotherapy clinical response. Outcome: no signal. Reason: baseline TCR clonality, diversity, and CD8+ ratios lacked statistically significant association with treatment outcomes

Explorations in cancer genomics and tumor immunology through analysis of next-generation sequencing data · Harvard · PhD

Tried and failed

immunophenotyping immune cell subsets for biomarker discovery applied to allograft rejection patient cohorts. Outcome: no signal. Reason: No statistically significant difference in specific regulatory T cell frequencies across clinical rejection groups

Human Leukocyte Antigen-E-restricted Killer Immunoglobulin-like Receptor-expressing CD8+ Regulatory T cells in Allograft Rejection · Harvard · Master's

Tried and failed

polyclonal superantigen stimulation assay applied to differentiating autoimmune vs inflammatory disease cohorts. Outcome: no signal. Reason: general T cell activation levels did not differ significantly between MS and disease controls

T Cell Responses In Pediatric-Onset Multiple Sclerosis: A Unique Window Into Early Disease · Penn · PhD

Considered and rejected

Considered and rejected: Subtracting baseline plasma cytokine concentrations from culture supernatant cytokine levels was omitted because plasma cytokine concentrations were not available for every subject

Analyse zu Zytokinmuster der T-Helferzellsubpopulationen bei Patienten mit Systemischer Sklerose vor und nach autologer Stammzelltransplantation · Tübingen · PhD

Lost to a baseline

Lack of a mock-infected cell culture supernatant experimental control in the Luminex assay to establish baseline cytokine/chemokine values in human fibroblasts

Characterization of Dengue Virus Serotype 1 and 2 Infection in Human Dermal Fibroblasts · Harvard · Master's

Considered and rejected

Considered and rejected: Rejected relying on standard antibody immunostaining for quantifying local Osm expression in spinal cords due to diffuse extracellular staining of secreted cytokines, choosing RNAscope in situ hybridization instead.

Dectin-1 Signaling in Central Nervous System Autoimmunity · Duke · PhD

Tried and failed

cytokine profiling of tissue explants applied to bacterial gastrointestinal infection model. Outcome: no signal. Reason: no significant changes detected across panel of target cytokines at selected post-infection timepoints

Temporal responses of the gastrointestinal tract to Citrobacter rodentium infection · Imperial · PhD

Tried and failed

multiplex cytokine profiling of tissue explants applied to early bacterial infection tissue response. Outcome: no signal. Reason: no significant differences in cytokine or chemokine levels across strains at early timepoints

Innate immunological contributions to severe C. rodentium infection · Imperial · PhD

Tried and failed

RT-qPCR quantification of cytokine mRNA expression applied to delayed-type hypersensitivity in knockout mice. Outcome: no signal. Reason: high intra-group variability prevented the observed increase from reaching statistical significance

The Neuropilin-2 Axis Regulates Carcinogenesis and Immune Surveillance in the Oral Cavity · Harvard · Doctorate

Tried and failed

high-throughput screening with primary immune cells applied to co-culture functional genomics screens. Outcome: unstable. Reason: post-expansion cellular impurity and high donor-to-donor variability compromised assay reproducibility

Loss of Bromodomain-Containing Protein 9 (BRD9) Reprograms Tumor Response to Natural Killer (NK) Cell-Mediated Killing · Cornell · PhD

Lost to a baseline

Refined multivariable Cox model performed worse (attenuated HR and lost significance) than single stromal CD68+ / CD45RO+ models due to collinearity among immune variables.

Analysing the relationship between immune infiltration and tissue architecture in high grade serous ovarian cancer · Cambridge · PhD

Lost to a baseline

Immune features alone achieved higher hazard ratios in predicting overall survival in chemotherapy CSCC (HR=4.3) compared to the combined CollaTIL model (HR=2.54).

Artificial Intelligence-Based Phenotyping of the Tumor Microenvironment in Hematoxylin and Eosin-Stained Images of Solid Tumors · Georgia Tech · PhD

Lost to a baseline

The full multi-compartment machine learning panel did not show a statistically significant AUC improvement over single-compartment plasma brain-derived protein panels (z = 1.11, p = 0.27) or plasma cytokine panels (z = 1.1, p = 0.26).

Evaluating Brain Derived Extracellular Vesicles As Diagnostic Biomarkers Of Traumatic Brain Injury · Penn · PhD

Left open

Evaluate IL-1α, IL-13, IL-17, and GROα/KC in CSF or blood serum as biomarkers of TBI severity and outcome. Blocker: Requires wet lab access, animal or clinical biofluid samples (CSF/serum), and assay equipment to measure cytokine levels

Profiling the neuroimmune cascade after repetitive mild traumatic brain injury · Georgia Tech · PhD

Left open

Combine multiple systemic inflammatory markers and pleiotropic cytokine genetic instruments to construct a multi-marker proxy for chronic low-grade inflammation. Blocker: Requires access to individual-level or comprehensive multi-cytokine cohort data (like UK Biobank) and specific methodology for multi-marker weighting is unspecified.

Multi-omics approach to explore the effects of chronic low-grade inflammation marked by c-reactive protein · Imperial · PhD

Left open

Measure secreted cytokine and chemokine protein levels via ELISA across infection timepoints in infected cell cultures and murine models. Blocker: Requires a wet lab, biological samples, infection models, and ELISA reagents

Characterizing the role of Staphylococcus aureus V8 protease in skin barrier damage and neuroimmune responses during host-pathogen interaction · Harvard · Master's

Left open

Profile cytokine secretomes and determine pyroptosis thresholds in WT versus Gsdmd-/- microglia and peripheral macrophages. Blocker: Requires primary mouse microglia, macrophages (WT and Gsdmd-/-), and wet-lab biological assays (e.g., cytokine profiling, IncuCyte).

The Role of Gasdermin D in Escherichia Coli K1 Bacterial Brain Infections · Harvard · Master's

Left open

Differentiate causal driver proteins from downstream inflammatory markers in severe COVID-19 using expanded multi-omics datasets and Mendelian randomisation. Blocker: No specific expanded omics datasets, cohort targets, or analytical framework are defined.

Using multi-omics to investigate the host response to COVID-19 · Imperial · PhD

Left open

Develop an interpretation method for feline-specific multiplex cytokine profiling data in cheetah serum. Blocker: Requires cheetah serum samples, wet lab cytokine profiling data, and veterinary immunology expertise

Multidisciplinary approach to Cheetahs affected by gastrointestinal disease: study of the immune profile and of the fecal proteome · University of Camerino · PhD

Left open

Characterize immune cell phenotypes using CyTOF or single-cell multi-omics methods like CITE-seq and SEC-seq. Blocker: Requires wet lab experimental facilities, biological samples, and specialized instrumentation (e.g., CyTOF/Hyperion Imaging System, single-cell sequencing platforms).

Utilizing Combinatory Adjuvant-Loaded Chitosan-Derived Nanoparticles for a Joint SARS-CoV-2/Influenza Vaccine · Georgia Tech · PhD

Left open

Validate SpatialVizScore using larger clinical multiplex imaging cohorts with complete immune checkpoint inhibitor response and long-term survival data. Blocker: Requires multiplexed imaging cohorts with matched immunotherapy response and survival outcomes

Deciphering Spatial Immune Interactions in Health and Disease using Multiplexed Imaging Tools · Georgia Tech · PhD

Left open

Incorporate multi-scale modalities including imaging phenotypes, tumour microenvironment, immune status, and longitudinal trajectories into the chemotherapy response prediction model. Blocker: No specific multi-modal patient datasets or integration architecture specified

Predicting cancer patient response to chemotherapy using machine learning from small data · Imperial · PhD

Left open

Integrate multi-omic profiling to correlate peripheral immune DNA repair capacity with tumor tissue repair signatures. Blocker: Requires matched patient samples with multi-omic profiling and wet-lab functional DNA repair capacity measurements

Precision Medicine: Biomarkers of Genome Integrity in Guiding Better Lung Cancer Outcomes · Harvard · PhD