Functional Biomarkers & Paradigm

18

Terms

Term	Description
Colocalization 70–100 nm Resolution	Proteins in same ~200 nm region (optical limit). Suggests proximity but cannot confirm molecular-scale engagement.
CXCL10 C-X-C Motif Chemokine Ligand 10 / Interferon gamma-Induced Protein 10 (IP-10)	Dual-function CXCR3 chemokine combining T cell recruitment with angiostatic activity—the most broadly validated serum ...
CXCL11 C-X-C Motif Chemokine Ligand 11 / Interferon-Inducible T cell Alpha Chemoattractant (I-TAC)	Highest-affinity CXCR3 ligand with dual CXCR3/CXCR7 signaling—paradoxically recruits anti-tumor T cells while driving ...
CXCL9 C-X-C Motif Chemokine Ligand 9 / Monokine Induced by Gamma-Interferon (MIG)	IFN-γ-induced CXCR3 ligand that recruits CD8+ T cells to the tumor microenvironment—a biomarker of inflamed tumors wi...
Dendritic Cells Dendritic Cells (DCs)	Antigen-presenting cells that prime T cells–critical for initiating anti-tumor immunity.
Functional Biomarkers Activity-Based Biomarkers	Biomarkers measuring protein activity/interactions rather than expression. Predict outcomes where expression-based marke...
Functional Measurement vs Expression	The core distinction: expression tells you proteins are present, functional measurement tells you they are actually work...
MSI Microsatellite Instability	DNA repair defect causing hypermutation–strong predictor of checkpoint inhibitor response.
Neoantigen Tumor Neoantigen	Tumor-specific mutant peptides recognized by T cells–the targets that make immunotherapy work.
PI3K/Akt Pathway Phosphoinositide 3-Kinase / Protein Kinase B Signaling Pathway	Major oncogenic pathway where FRET-measured Akt activation predicts survival while expression-based markers fail.
Protein Activation State	Whether a protein is functionally active—not just present. The difference between a car in the garage and a car with t...
Protein-Protein Interaction PPI	Physical binding between proteins at 1–10 nm distances–what FRET actually measures, revealing functional engagement....
Proximity Ligation Assay PLA - Duolink	Proximity ligation detecting targets within ~40 nm. Better than colocalization but not true molecular-scale detection.
Spatial Biology Spatial Proteomics - Spatial Omics	Field combining molecular analysis with tissue architecture. FLIM-FRET adds functional dimension–where proteins intera...
T Cell Exhaustion T Lymphocyte Exhaustion	Dysfunctional T cell state with high checkpoint expression–the target of checkpoint immunotherapy.
TMB Tumor Mutational Burden	Mutation count per megabase–predicts ICI response but doesn't measure actual checkpoint engagement.
Tregs Regulatory T Cells	Immunosuppressive T cells that tumors recruit to dampen anti-tumor immunity.
Two-Site Assay Coincidence Detection - Dual-Antibody Assay	Assay requiring two antibodies to bind for signal generation–provides inherent specificity for detecting protein compl...