CD58 and cancer: The CD58−CD2 immune checkpoint constitutes a vital component in the immunological synapse that integrates signals for optimal T cell activation26,44,45 and cytolytic activities against tumor cells from various cancer types.17,27,29–31 Recent studies have linked the loss of CD58 to resistance in T cell-based cancer immunotherapies in both hematopoietic and solid cancers.16,17 However, aside from inactivating genetic mutations frequently found in lymphomas, the regulatory mechanisms underlying CD58 loss remain largely unclear.