T cell expansion criteria
To identify treatment-expanded T cell clones, we used an adapted Fisher’s exact test and computed We implemented this by rescaling the repertoire size of the initial sample by half, to effectively reduce the sample size and the number of cells not belonging to the clone in question. We computed this as a Fisher’s exact test (implemented from scipy.stats.fisher_exact) using the categorical table supplied in Extended Data Table Clones that had a fold change <2 (that is, We applied this T cell clone expansion Atezolizumab response: to determine whether atezolizumab expanded T cell clones (Extended Data Fig. Autogene cevumeran response with priming doses: to determine whether autogene cevumeran expanded T cell clones, we imposed two criteria: (1) a quality control requirement that a T cell clone must have a minimum of three reads in at least two samples, and (2) the T cell clone must not be observed before vaccination (0 cells in all samples taken until the day of but before the first dose of autogene cevumeran).Then, for clones that passed these criteria (as defined above), we compared the number of cells of a particular T cell clone in a blood sample taken after atezolizumab and before vaccination to the number of cells of that T cell clone in any blood sample taken until the day of but before the first dose of mFOLFIRINOX. We further assigned an expansion We then considered that a patient had a response to autogene cevumeran if any T cell clone significantly expanded (For 50% of the responders (Autogene cevumeran response with a booster dose: to determine whether an autogene-cevumeran-expanded clone further expanded after the booster dose, we used a standard Fisher’s exact test, with no additional fold change criteria, to compare the clone sizes in samples taken immediately before booster administration to samples from the first follow-up after the booster. As we had previously identified these clones and assessed each one independently, we did not use any multiple hypothesis adjustment and set a significance threshold of 