Figure 3.

T Cell Receptor Repertoire Features and Dynamics during Immune Checkpoint Blockade Differentiate Tumors of Responders from Non-responders

(A) Differential abundance analysis employing the number of TCR clones revealed an enrichment of unique TCR rearrangements in tumors of responding patients (FDR-adjusted p = 0.0018).

(B) Dynamic shifts in the TCR repertoire composition on therapy were reflective of clinical outcome, such that tumors of responders harbored a higher fraction of expanding and regressing clones. A representative example of TCR repertoire reshaping is shown in (B) for patient 20002, who achieved a complete response on ipilimumab and nivolumab.

(C) Overall, the fraction of expanding and regressing TCR clones was significantly higher in responders compared to non-responders (FDR p = 0.02 for both fractions of responding and regressing clones).

(D) Representative example of TCR repertoire dynamics for a patient experiencing disease progression on the ipilimumab/nivolumab arm; a less dynamic repertoire is observed, denoted by a significantly lower number of clonotypic expansions and regressions after therapy initiation.