CTLA4 and neoplasm: Consistent with the clinical observations of hyperprogression in response to nivolumab plus ipilimumab, the preclinical combination of anti-PD-1 plus anti-CTLA-4 (ICT) resulted in significantly increased primary tumor mass (Fig. 4c–e), as well as a greater metastatic tumor burden compared with IgG control, particularly in the lungs and liver (Fig. 4f, j).