Fig. 2: Development of MANAscore using patient-specific thresholds.
A Expression level of three genes previously reported to mark tumor-reactive vs bystander CD8+ TIL in validated MANA-, EBV- and InfluenzaA-specific TIL in the Oliveira et al melanoma dataset. B Receiver operating characteristic (ROC) curves for the performance of different models, including imputed MANAscore (MANAscore_i), non-imputed MANAscore (MANAscore_ni), original NeoTCR8 score (calculated by scGSEA), imputed CXCL13 single gene model (CXCL13_i), and non-imputed CXCL13 single gene model (CXCL13_ni) on the melanoma test data. Test data consisted of 20% of the validated MANA- and EBV-/InfluenzaA- specific CD8+ TIL (n = 838 tumor-reactive and 573 bystander TIL) and all melanoma associated antigen (MAA)-specific and 20% of the EBV-/InfluenzaA-specific CD8+ TIL from melanoma patient p2 (n = 283 tumor-reactive and 204 bystander TIL). C ROC curves for the performance of the MANAscore_i, MANAscore_ni, NeoTCR8, CXCL13_i, and CXCL13_ni models on the validation datasets. Validation was performed on 72 MANA-specific and 18 bystander CD8+ TIL from NSCLC patient MD01-004 and on 38 MANA-specific and 445 bystander CD8+ TIL from NSCLC patient MD01-005 from Caushi et al. D Feature plot for MANAscore_i (left) and MANAscore_ni (right) on CD8 TIL with unknown antigen specificity in the Caushi et al NSCLC cohort. MANAscore ranges from 0 (blue) to 1 (red). E Scatter plot of MANAscore_i and MANAscore_ni in selected NSCLC patient tumors. Cutoffs were set to define MANAscorehi CD8+ TIL by assessing distribution of these two scores at the patient level. Red dotted lines indicate the thresholds for MANAscorehi in the imputed and non-imputed models, the linear correlation of these two scores was marked in green, Pearson’s correlation coefficient is added. F Cell type contribution to MANAscorehi CD8+ TIL.
