MYC regulates the antitumor immune response through CD47 and PD-L1

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Science  08 Apr 2016:
Vol. 352, Issue 6282, pp. 227-231
DOI: 10.1126/science.aac9935

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Oncogene control of antitumor immunity

Recent clinical success of cancer immunotherapy has intensified interest in how tumors normally evade the immune response. Whether and how oncogenes contribute to this process are not well understood. In a study of mice, Casey et al. found that the MYC oncogene, which is aberrantly activated in many human cancers, up-regulates the expression of genes encoding proteins that dampen the antitumor response. These include two proteins that are often overexpressed on tumor cells and that serve as immune checkpoints. One of them (PDL1) sends to the immune system a “don't find me” signal, and the other (CD47) sends a “don't eat me” signal. Thus, therapies aimed at suppressing MYC may help promote an immune response against tumors.

Science, this issue p. 227


The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death–ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 messenger RNA and protein. MYC was found to bind directly to the promoters of the Cd47 and Pd-l1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed, and tumors continued to grow. Thus, MYC appears to initiate and maintain tumorigenesis, in part, through the modulation of immune regulatory molecules.

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