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. Here, CD58 is linked to lymphoma.