Natural compound inducers of immunogenic cell death

  • Marc DiederichEmail author


Accumulating evidence shows that the anti-cancer potential of the immune response that can be activated by modulation of the immunogenicity of dying cancer cells. This regulated cell death process is called immunogenic cell death (ICD) and constitutes a new innovating anti-cancer strategy with immune-modulatory potential thanks to the release of damage-associated molecular patterns (DAMPs). Some conventional clinically-used chemotherapeutic drugs, as well as preclinically-investigated compounds of natural origins such as anthracyclines, microtubule-destabilizing agents, cardiac glycosides or hypericin derivatives, possess such an immune-stimulatory function by triggering ICD. Here, we discuss the effects of ICD inducers on the release of DAMPs and the activation of corresponding signaling pathways triggering immune recognition. We will discuss potential strategies allowing to overcome resistance mechanisms associated with this treatment approach as well as co-treatment strategies to overcome the immunosuppressive microenvironment. We will highlight the potential role of metronomic immune modulation as well as targeted delivery of ICD-inducing compounds with nanoparticles or liposomal formulations to improving the immunogenicity of ICD inducers aiming at long-term clinical benefits.


Immunogenic cell death Chemotherapy Immune response CD8+ T-cells Regulatory T cells Combination treatments Nano-formulation Natural products Immunity Anti-cancer immune response 



The author thanks Dr. Flavia Radogna for proofreading and helpful comments. MD’s research at SNU is supported by National Research Foundation (NRF) [Grant Number 019R1A2C1009231] and by a grant from the MEST of Korea for Tumor Microenvironment Global Core Research Center (GCRC) [Grant Number 2011-0030001]. Support from Brain Korea (BK21) PLUS program and Creative-Pioneering Researchers Program at Seoul National University [Funding number: 370C-20160062] are acknowledged. MD also thanks the “Recherche Cancer et Sang” foundation, “Recherches Scientifiques Luxembourg” association, “Een Häerz fir kriibskrank Kanner” association, Action LIONS “Vaincre le Cancer” association and Télévie Luxembourg.

Compliance with ethical standards

Conflict of interest

The author declares no conflict of interest.


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© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of PharmacySeoul National UniversitySeoulSouth Korea

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