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Page 22 of 38 J Cancer Metastasis Treat 2020;6:5 I http://dx.doi.org/10.20517/2394-4722.2020.13

a potent immune-mediating reaction. Several parameters determine whether a compound can act as an
immunogenic cell death (ICD) inducer including the nature of the inducer, the premortem stress pathways,
the cell death pathways, the intrinsic antigenicity of the cell, and the potency and availability of an immune
[2]
cell response .
Experimental procedure: We used a multifactor approach: (1) detecting endoplasmic reticulum (ER) stress
markers; (2) investigating and quantifying caspase-dependent or independent cell death; (3) measuring the
release of danger associated molecular patterns; (4) quantifying phagocytosis of compound-treated cells by
both murine and human monocyte-derived macrophages; (5) performing colony formation assays and in
vivo zebrafish xenografts; and (6) performing vaccination assays with immunocompetent mice.

Results: We identified ICD-inducing capacities of old (coumarinics) and novel (stemphol and cardiac
glycoside UNBS1450) inducers of immunogenic cell death together with venetoclax and experimental BH3
mimetics. We detected their capacity to trigger synergistic cell death in myeloid leukemia in an attempt
to overcome apoptosis-resistant myeloid leukemia alone or in combination with other chemotherapeutic
compounds.

Conclusion: The identification of hallmarks of ICD is important in determining the prognostic biomarkers
[3]
for new therapeutic approaches and combination treatments . In myeloid leukemia, combination
[5]
[4]
treatments of ICD-inducing pharmacological agents with Venetoclax showed positive synergistic effects
allowing to confer immunogenicity to otherwise cytotoxic non-immunogenic treatments.

REFERENCES
1. Radogna F, Diederich M. Stress-induced cellular responses in immunogenic cell death: Implications for cancer immunotherapy. Biochem
Pharmacol 2018;153:12-23.
2. Mazumder A, Lee JY, Talhi O, Cerella C, Chateauvieux S, et al. Hydroxycoumarin OT-55 kills CML cells alone or in synergy with
imatinib or Synribo: Involvement of ER stress and DAMP release. Cancer Lett 2018;438:197-218.
3. Ji S, Lee JY, Schrör J, Mazumder A, Jang DM, et al. The dialkyl resorcinol stemphol disrupts calcium homeostasis to trigger programmed
immunogenic necrosis in cancer. Cancer Lett 2018;416:109-23.
4. Diederich M, Muller F, Cerella C. Cardiac glycosides: From molecular targets to immunogenic cell death. Biochem Pharmacol
2017;125:1-11.
5. Cerella C, Gaigneaux A, Mazumder A, Lee JY, Saland E, et al. Bcl-2 protein family expression pattern determines synergistic pro-apoptotic
effects of BH3 mimetics with hemisynthetic cardiac glycoside UNBS1450 in acute myeloid leukemia. Leukemia 2017;31:755-9.

31. The role of autophagy in inflammatory cytokines-induced epithelial to mesenchymal
transition in cancer

1
1
Chiara Vidoni , Alessandra Ferraresi , Eleonora Secomandi , Letizia Vallino , Suyanee
1
1
Thongchot , Danny Dhanasekaran , Ciro Isidoro 1
2
1
1 Department of Health Sciences, Università del Piemonte Orientale, Novara 28100, Italy.
2 Stephenson Cancer Center, Oklahoma University Health Science Center, Oklahoma City, OK 73104, USA.
The peculiar hallmark distinguishing malignant from benign tumors is the ability of the former to invade
the extracellular matrix and metastasize to near and distant organs. This process implies an epigenetic
change in the expression of genes that leads to a reversible phenotypic change of the cancer cells from
epithelial-like to mesenchymal-type known as epithelial-to-mesenchymal transition (EMT). The tumor
microenvironment plays a pivotal role in this process, the major players being the pro-inflammatory
cytokines IL-6 and IL-8 released by cancer associated fibroblasts, immune cells (M2 macrophages), and
cancer cells themselves.