CALR and cancer: Thus, CALR exposure and ATP secretion are required for the full-blown immunogenicity of cancer cells succumbing to hypericin-based PDT, but this can occur independently of eIF2α phosphorylation and autophagy activation.178 203 Likewise, neoplastic cells succumbing to necroptosis-driven ICD release ATP and HMGB1, but CALR is exposed at low levels on the plasma membrane and ISR activation appears to be dispensable.59 204