Extended Data Fig. 1. PD-L2 is upregulated in human and murine senescent cancer cells.
(a) Drug class enrichment analysis for human PDCD1LG2 (PD-L2). P = 0.0013 for cell cycle, P = 8.3 · 10-06 for DNA damage, P = 0.0003 for cytoskeleton. (b) PD-L1/2 mRNA expression in human cancer cell lines treated with palbociclib. (c) PD-L1/2 mRNA expression in human cancer cell lines after treatment with doxorubicin or palbociclib. (d) PD-L1/2 mRNA expression in murine cancer cell lines treated with doxorubicin. N = 3 experiments for (b-d). (e) Normalized PD-L1/2 mRNA expression measured by RNA sequencing. N = 4 biological replicates. (f) Growth curve and representative whole mount beta-galactosidase stainings of SK-MEL-103 xenografts in nude mice, untreated or treated with 100 mg/kg oral palbociclib, daily, once tumors reached 150 mm3 (day 7-10). (g) PD-L1/2 mRNA expression in SK-MEL-103 cells treated with doxorubicin and the IKK inhibitor BAY 11-7082 (3 µM, 24 h). N = 11 control mice and 14 palbociclib-treated mice. (h) PD-L1/2 mRNA expression in SK-MEL-103 cells treated with TNF-α (100 ng/ml, 3 days). N = 3 experiments for (g-h). Data are presented as mean ± SEM. Two-sided t-tests or 1 way ANOVA with Tukey post-test were applied. For all the experiments in culture, senescence was induced with 200 nM doxorubicin for 48 h, 5 µM palbociclib for 7 days or 12 mU bleomycin for 48 h. Senescence was evaluated at day 7.