CTLA4 and neoplasm: In this transition, the increase in the cytolytic marker perforin-1 (PRF1) at the gene expression level is accompanied by a potential immunoregulatory response involving upregulation of immune checkpoints including CD274/PD-L1, LAG3, CTLA4, BTLA, TIGIT and others (figure 6F), as described previously.30 A timely identification of this immunoregulatory response after RT/CRT may provide a therapeutic opportunity to further enhance tumor response by the additional adjuvant use of immune checkpoint inhibitors.