Impact of HGBL biology on efficacy of CAR T cells. Proposed impact of HGBL biology on efficacy of anti CD19 CAR T cells. HGBL may downregulate MHC-class II and PD-L1 antigens, which suppress CAR T cells via LAG-3 and PD-1, potentially leading to less T-cell exhaustion. Tumors that are resistant to CAR T cells have more activation of the immune microenvironment signature, which may be decreased in HGBL. Aberrations of p53 can increase tumor cell survival through downregulation of interferon signaling, induction of tumor-site immune privilege, and inhibition of extrinsic apoptosis.