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Fig. 6 | Genome Biology

Fig. 6

From: Clonal tracing reveals diverse patterns of response to immune checkpoint blockade

Fig. 6

Mathematical modeling reveals little contribution of ICB-resistant clones to the ICB resistance by the bulk tumor. a Scheme of the mathematical modeling of tumor clonal constitution. The fitness advantage of a clone (xk) can be expressed in a formula containing the proliferation and death rate of the bulk population (bp and dp, respectively), time of growth (t), and frequency of this clone at tumor harvest (fk). b The cumulative frequencies of clones belonging to each cluster learned from the mathematical model in groups treated by control IgG, anti-PD-1, or anti-CTLA4 (mean ± SD). c The cumulative frequency of clones belonging to cluster 5 or 6 in b is significantly higher in ICB responders. The cumulative frequency of clones belonging to cluster 1, 2, or 3 in b is significantly higher in non-responders (mean ± SD; **P < 0.01, ***P < 0.001; one-way ANOVA with Benjamini-Hochberg post-test multiple comparison). “res” are responders and “non” are non-responders. d, e Cancer cell-intrinsic resistance signatures derived from line B04 or B64 significantly correlate with better ICB response within d on-treatment samples in the Riaz et al. study [54] and e post-treatment samples in the Nathanson et al. study [82] (mean ± SD; two-sided t test). f, g Cancer cell-intrinsic resistance signatures derived from line B04 or B64 correlate with intra-tumoral cytolytic activity from multiple clinical studies

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