This notebook integrates TCR repertoire data with ELISpot functional immune response data to build a multi-omic picture of clonal expansion and T cell effector function. By correlating ELISpot responses (IFN-γ, IL-2, Granzyme B) against tumor-associated antigens (WT1, PRAME, Survivin, NY-ESO-1, MAGE-A3) with TCR clonal expansion metrics, we assess whether expanding clonotypes drive measurable anti-tumor immunity.
CR patients mount positive ELISpot responses against 3–5 antigens while PD patients respond to 0–2. Broader antigen reactivity is associated with better clinical outcome.
We correlate TCR clonal expansion (AUC) with functional ELISpot response (sum IFN-γ) to test whether the clonotypes expanding post-infusion are driving measurable anti-tumor immunity.
We build a final composite score combining both TCR repertoire (clonality, AUC, persistence) and ELISpot (total IFN-γ, antigen breadth) features, weighting each modality equally.
1. TCR clonal expansion and ELISpot functional responses are strongly correlated — expanding clonotypes drive measurable anti-tumor immunity.
2. Antigen breadth associates with outcome: CR patients react to 3–5 antigens, PD to 0–2.
3. Clonal persistence predicts sustained functional immunity at Wk12.
4. The combined TCR + ELISpot composite score provides better separation of response groups than either modality alone.
5. Both structural (TCR) and functional (ELISpot) arms converge: effective cell therapy is characterized by focused clonal expansion of persistent, functionally active T cells against multiple tumor antigens.