Extended Data Fig. 10: (Related to Specific public T cells are linked to survival.) Public and Private TCR clonotypes in rGBM IDHwt (a, b), PBMCs (c, d) and combined (e, f).
From: Clinical trial links oncolytic immunoactivation to survival in glioblastoma
Jaccard Indices heatmaps (a, c, e) and Pearson’s correlation coefficient maps (b, d, f) are shown for amino acid-based shared (public) or unshared (private) TCRs between samples. For Jaccard maps (a, c, e), colour in box provides a gradient with white indicating no shared TCRs and increasing shades of blue indicating more shared TCRs between tumours. For (a-f) the top row denotes survival for each subject with the red bars denoting the SS (short survivors defined as survival <1-year post CAN-3110) and green bars the LS (long survival defined as survival >1-year post CAN-3110) subjects and the small y axis showing survival days. The right Y and X axes denote each subject with paired Pre- and Post-CAN-3110 rGBM IDHwt, ordered based on respective overall survival time. The number of private TCRs is shown in the bar graphs to the right of the heatmaps. For (b, d, f), each box represents a neutral (white), negative (red spectrum) or positive (blue spectrum) Pearson correlation coefficient between pre, post-CAN 3110 Tumour (a, b), PBMCs (c, d), or all combined (e, f). In TILs, there were 5 TCRs publicly shared amongst 4 patients, 45 amongst 3 patients, and 792 between 2 patients. The remaining 41,756 tumour TCRs were private (i.e., not shared between patients). Grey boxes denote no shared TCRs between samples. Asterisks inside boxes denote significant Pearson’s correlations p < 0.05, ** p < 0.01, *** p < 0.001 (2-sided, based on t-distribution). Note that 042 and 054 are the same individual treated at two different timepoints with CAN-3110. (g, h) PBMC TCRs for which post-CAN-3110 change in productive frequency associates with post-CAN-3110 survival (FDR ≤ 0.05 based on Pearson’s correlation p values calculated 2-sided using t-distribution) in rGBM IDHwt with available TCRβ sequences (n = 21 interventions/20 patients). Patient 045 excluded due to early non-GBM related mortality. TCRβ sequences were included if present in PBMCs from 21 interventions with a median read count of at least 2 pre- or post-CAN-3110. Pearson’s r, p (2-sided, based on t-distribution), and FDR are included in each plot. (g) CASSLGGNTEAFF37,38 was detected in the TIL TCRs of two patients post CAN-3110. (h) CASSSSTDTQYF39 was detected in the TIL TCRs of one patient pre CAN-3110.
