Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.

For PD-1, we found an increasing trend in the percentage of anti-PD-1 antibody bound cells with longer treatment duration when comparing nodules obtained from EGFR TL and Kras mice that had received from 2–8 weeks of therapy ( Supplementary Fig. 1e ), suggesting that PD-1 blockade could enrich for PD-1 expression on TILs.

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We also evaluated PD-L1 expression levels in human monocytes (CD33 + CD66b − CD14 + ) and found a nonsignificant trend towards increased PD-L1 expression in the anti-PD-1-resistant samples ( Supplementary Fig. 7f ).

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