Extended Data Fig. 10: Analysis of human CD8⁺ T cell clusters.

Association of human CD8⁺ T cell clusters corresponding to mouse reference with response in tiragolumab plus atezolizumab Ph1b and Ph2 NSCLC clinical trials. a. scRNA-seq of 144,413 human CD8⁺ T cells from blood of patients in a Ph1b NSCLC study of tiragolumab plus atezolizumab (T + A). Human genes were renamed to their mouse ortholog (if present) and gene expression was normalized before sample integration and projection onto a mouse CD8⁺ T cell reference UMAP. b. Predicted cell type score for mapped human CD8⁺ T cells for each assigned mouse CD8⁺ T cell reference cluster. c. Frequencies of human predicted clusters in patients with complete or partial response (CRPR) compared to stable or progressive disease (SDPD) on cycle 2 day 1 of treatment with T + A in the Ph1b study. Percent total was calculated as the percentage of the cluster in total CD8⁺ T cells for each patient. d. Forest plot comparing high or low expression of the top corresponding human 18-20 signature genes (signature gene score) from each mouse CD8⁺ T cell cluster or CD8A and their association with overall survival (OS) hazard ratio (HR) T + A or placebo plus atezolizumab (P + A) treatment groups in Ph2 CITYSCAPE. Mean HR with 95% confidence intervals and p-values are shown. e, Kaplan-Meier curves showing OS probability in P + A or T + A treatment groups dichotomized on the basis of high or low CD8⁺ T cell cluster gene scores from each reference cluster. p-value is from log-rank test with null hypothesis that there is no difference between the groups. f. Kaplan-Meier curves comparing progression-free survival (PFS, left) or OS (right) in patients from the phase 3 NSCLC OAK study who received atezolizumab monotherapy. Patients were dichotomized by median gene score calculated using the average expression of the CD8 gene panel comprised of CXCR3, CXCR6 and CCL5.