Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called "damage-associated molecular patterns," DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from patients with acute myeloid leukemia (AML) exposed multiple DAMPs, including calreticulin (CRT), heat-shock protein 70 (HSP70), and HSP90 on their plasma membrane irrespective of treatment. In these patients, high levels of surface-exposed CRT correlated with an increased proportion of natural killer cells and effector memory CD4+ and CD8+ T cells in the periphery. Moreover, CRT exposure on the plasma membrane of malignant blasts positively correlated with the frequency of circulating T cells specific for leukemia-associated antigens, indicating that ecto-CRT favors the initiation of anticancer immunity in patients with AML. Finally, although the levels of ecto-HSP70, ecto-HSP90, and ecto-CRT were all associated with improved relapse-free survival, only CRT exposure significantly correlated with superior overall survival. Thus, CRT exposure represents a novel powerful prognostic biomarker for patients with AML, reflecting the activation of a clinically relevant AML-specific immune response.

• MeSH
• akutní myeloidní leukemie farmakoterapie   genetika   imunologie   metabolismus   MeSH
• alarminy metabolismus   MeSH
• blastická krize imunologie   patologie   MeSH
• buněčná smrt MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• fenotyp MeSH
• genetická transkripce MeSH
• imunita MeSH
• kalretikulin metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• proporcionální rizikové modely MeSH
• proteiny tepelného šoku HSP70 metabolismus   MeSH
• proteiny tepelného šoku HSP90 metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• stanovení celkové genové exprese MeSH
• Th1 buňky imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alarminy MeSH
• CALR protein, human MeSH Prohlížeč
• kalretikulin MeSH
• proteiny tepelného šoku HSP70 MeSH
• proteiny tepelného šoku HSP90 MeSH

Circulating immune complexes (CIC) were measured at the time of diagnosis in 81 patients with acute leukemia or blast crisis of chronic myeloid leukemia using precipitation by 3.75% polyethyleneglycol. Elevated CIC levels did not adversely influence complete remission duration and survival, patients with normal CIC levels exhibited mostly shorter remission and survival than those with elevated or borderline levels. No significant correlation was observed between CIC levels and Hb, WBC, CBC, platelet count, age, serum bilirubin, total protein, fibrinogen, AST and ALT levels, presence of hepatosplenomegaly and/or lymphadenopathy, HbSAg positivity, complete remission duration and survival. The lack of correlation may be caused by altered immune response in leukemic patients, but the obtained results may also be affected by the nonspecific nature of the method used for the detection. Simultaneous detection of CIC levels by multiple tests and evaluation not only of the number but also of the composition and size of CIC may decrease the incidence of false results. Nevertheless, only the establishment of antigen-specific assays may resolve the controversies in the detection of CIC and thus contribute to a more precise assessment of the role of CIC in prognosis of cancer, as well as to the verification of reliability of using CIC as a tumor marker.

• MeSH
• akutní lymfatická leukemie imunologie   MeSH
• akutní myeloidní leukemie imunologie   MeSH
• blastická krize imunologie   MeSH
• chronická myeloidní leukemie imunologie   patologie   MeSH
• dospělí MeSH
• imunokomplex metabolismus   MeSH
• indukce remise MeSH
• leukemie imunologie   mortalita   MeSH
• lidé MeSH
• počet leukocytů MeSH
• prognóza MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunokomplex MeSH