Comparative analysis of gene expression in tumors responding and non-responding to anti-CTLA-4 in a preclinical study of melanoma

To investigate the diverse responses of the M4 mouse melanoma to immune checkpoint inhibitors, the tumors responding (R) and nonresponding (NR) to anti-CTLA-4 from a preclinical study of M4 melanoma were subjected to mRNA sequencing. The differentially expressed genes were analyzed to identify the signaling pathways that asscoiated with the therapeutic responses of the tumors. 40 C57BL/6 mice were implanted with the M4 melanoma cell line (B2905). When the tumors reached to average size of 75 mm^3, they were randomized to three groups: (1) 5 mice left untreated; (2) 5 mice treated with isotype control IgG2b; (3) 30 mice treated with anti-CTLA-4. The antibodies were given twice a week for two weeks. 20 tumors of the group (3) and 5 tumors of the group (2) were harvested for RNA sequencing. In the 10-11 days after the last dose of treatment, tumors were identified as nonresponders, responders, and stable disease if their sizes continued to increase, decrease, and remain stable, respectively.