Immunogenic apoptosis in human acute myeloid leukemia (AML): primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis

Fredly, Hanne; Ersvær, Elisabeth; Gjertsen, Bjørn Tore; Bruserud, Øystein

doi:10.3892/or.2011.1229

Cited by 22 publications

(26 citation statements)

References 19 publications

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“…Apoptotic AML cells collected during in vivo therapy with all- trans retinoic acid showed increased exposure of CRT during spontaneous in vitro apoptosis, suggesting that in vivo pharmacotherapy can induce ICD. 29 But the authors detected a wide variation of the level of CRT exposure between patients, which probably depends on individual patient characteristics. 29 It has also been shown that serum CRT levels are significantly higher in lung cancer patients after chemotherapy compared to untreated patients.…”

Section: Role Of Crt Surface Exposure During Icd In Cancer Treatmentmentioning

confidence: 98%

Many faces of DAMPs in cancer therapy

et al. 2013

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A new concept of immunogenic cell death (ICD) has recently been proposed. The immunogenic characteristics of this cell death mode are mediated mainly by molecules called ‘damage-associated molecular patterns' (DAMPs), most of which are recognized by pattern recognition receptors. Some DAMPs are actively emitted by cells undergoing ICD (e.g. calreticulin (CRT) and adenosine triphosphate (ATP)), whereas others are emitted passively (e.g. high-mobility group box 1 protein (HMGB1)). Recent studies have demonstrated that these DAMPs play a beneficial role in anti-cancer therapy by interacting with the immune system. The molecular pathways involved in translocation of CRT to the cell surface and secretion of ATP from tumor cells undergoing ICD are being elucidated. However, it has also been shown that the same DAMPs could contribute to progression of cancer and promote resistance to anticancer treatments. In this review, we will critically evaluate the beneficial and detrimental roles of DAMPs in cancer therapy, focusing mainly on CRT, ATP and HMGB1.

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Section: Role Of Crt Surface Exposure During Icd In Cancer Treatmentmentioning

confidence: 98%

Many faces of DAMPs in cancer therapy

et al. 2013

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“…The use of such an approach as a low-toxicity strategy in older patients is supported by several observations. First, primary human AML cells can undergo immunogenic apoptosis with exposure of calreticulin, and release heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90); this may initiate or enhance the development of antileukemic T cell reactivity [115]. Second, a prognostic impact of serum heat shock protein (HSP) levels has been suggested [116-119], possibly caused by soluble HSPs that facilitate immunogenic presentation of the client proteins.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents

2013

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Several new therapeutic strategies are now considered for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy, including modulation of protein lysine acetylation through inhibition of histone deacetylases (HDACs). These enzymes alter the acetylation of several proteins, including histones and transcription factors, as well as several other proteins directly involved in the regulation of cell proliferation, differentiation and apoptosis. Valproic acid (VPA) is a HDAC inhibitor that has been investigated in several clinical AML studies, usually in combination with all-trans retinoic acid (ATRA) for treatment of patients unfit for intensive chemotherapy, for example older patients, and many of these patients have relapsed or primary resistant leukemia. The toxicity of VPA in these patients is low and complete hematological remission lasting for several months has been reported for a few patients (<5% of included patients), but increased peripheral blood platelet counts are seen for 30 to 40% of patients and may last for up to 1 to 2 years. We review the biological effects of VPA on human AML cells, the results from clinical studies of VPA in the treatment of AML and the evidence for combining VPA with new targeted therapy. However, it should be emphasized that VPA has not been investigated in randomized clinical studies. Despite this lack of randomized studies, we conclude that disease-stabilizing treatment including VPA should be considered especially in unfit patients, because the possibility of improving normal blood values has been documented in several studies and the risk of clinically relevant toxicity is minimal.

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“…In AML cells, cytarabine, daunorubicin, all-trans retinoic acid (ATRA) and valproic acid were also found to induce increased calreticulin exposure (ecto-CRT) and release of HSP70 and HSP90, which indicating an induction of immunogenic apoptosis, although the level of CRT exposure/HSP release seems to depend on individual patients characteristics rather than the apoptosis-inducing drug [102]. Bortezomib had been showed to induce immunogenic death of human multiple myeloma, including primary tumor cells, which is dependent on cell-cell contact and linked to the expression of Hsp90 on the surface of dying cells [103]. More recently, diverse pro-apoptotic drugs, including topoisomerase II inhibitors, kinase inhibitors, and proteosome inhibitors have been shown to activate pannexin-1 channels and ATP release in Jurkat T cell acute lymphocytic leukemia model, which mediate immunogenic anti-tumor responses [104].…”

Section: The Role Of Autophagy Autophagy-associated Adaptive Immunitmentioning

confidence: 99%

Autophagy, autophagy-associated adaptive immune responses and its role in hematologic malignancies

et al. 2016

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Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder. In blood cancer cells, autophagy can either result in chemoresistance or induce autophagic cell death that may act as immunogenic. Based on the successful experimental findings in vitro and in vivo, clinical trials of autophagy inhibitor such as hydroxychloroquine in combination with chemotherapy in patients with blood cancers are currently underway. However, autophagy inactivation might impair autophagy-triggered anticancer immunity, whereas induction of autophagy might become an effective immunotherapy. These aspects are discussed in this review together with a brief introduction to the autophagic molecular machinery and its roles in hematologic malignancies.

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Immunogenic apoptosis in human acute myeloid leukemia (AML): primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis

Cited by 22 publications

References 19 publications

Many faces of DAMPs in cancer therapy

Many faces of DAMPs in cancer therapy

Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents

Autophagy, autophagy-associated adaptive immune responses and its role in hematologic malignancies

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