Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia

• Published in: Cell death & disease Vol. 1; no. 12; p. e104
• Main Authors: Wemeau, M, Kepp, O, Tesnière, A, Panaretakis, T, Flament, C, De Botton, S, Zitvogel, L, Kroemer, G, Chaput, N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2010; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/250/1933; 631/45/612/1234; 631/67/1059/99; 692/699/1541/1990/283/1897; Adult; Aged; Aged, 80 and over; Anthracyclines - therapeutic use; Antibodies; Antineoplastic Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Calreticulin - drug effects; Calreticulin - metabolism; Cell Biology; Cell Culture; Cohort Studies; Dendritic Cells - physiology; Eukaryotic Initiation Factor-2 - metabolism; Female; Humans; Immunity, Cellular - drug effects; Immunology; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Life Sciences; Male; Medicin och hälsovetenskap; Middle Aged; Original; original-article; Phagocytosis - drug effects; Phosphorylation; Survival Analysis; T-Lymphocytes - immunology; anthracyclines; acute myeloid leukemia; calreticulin exposure; T cells immunity
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2010.82

Experiments performed in mice revealed that anthracyclines stimulate immunogenic cell death that is characterized by the pre-apoptotic exposure of calreticulin (CRT) on the surface of dying tumor cells. Here, we determined whether CRT exposure at the cell surface (ecto-CRT) occurs in human cancer in response to anthracyclines in vivo , focusing on acute myeloid leukemia (AML), which is currently treated with a combination of aracytine and anthracyclines. Most of the patients benefit from the induction chemotherapy but relapse within 1–12 months. In this study, we investigated ecto-CRT expression on malignant blasts before and after induction chemotherapy. We observed that leukemic cells from some patients exhibited ecto-CRT regardless of chemotherapy and that this parameter was not modulated by in vivo chemotherapy. Ecto-CRT correlated with the presence of phosphorylated eIF2 α within the blasts, in line with the possibility that CRT exposure results from an endoplasmic reticulum stress response. Importantly, high levels of ecto-CRT on malignant myeloblasts positively correlated with the ability of autologous T cells to secrete interferon- γ on stimulation with blast-derived dendritic cell. We conclude that the presence of ecto-CRT on leukemia cells facilitates cellular anticancer immune responses in AML patients.