, Volume 14, Issue 4, pp 364–375 | Cite as

Immunogenic cell death modalities and their impact on cancer treatment

  • Oliver Kepp
  • Antoine Tesniere
  • Frederic Schlemmer
  • Mickael Michaud
  • Laura Senovilla
  • Laurence Zitvogel
  • Guido Kroemer
Cell Death and Disease


It is still enigmatic under which circumstances cellular demise induces an immune response or rather remains immunologically silent. Moreover, the question remains open under which circumstances apoptotic, autophagic or necrotic cells are immunogenic or tolerogenic. Although apoptosis appears to be morphologically homogenous, recent evidence suggests that the pre-apoptotic surface-exposure of calreticulin may dictate the immune response to tumor cells that succumb to anticancer treatments. Moreover, the release of high-mobility group box 1 (HMGB1) during late apoptosis and secondary necrosis contributes to efficient antigen presentation and cytotoxic T-cell activation because HMGB1 can bind to Toll like receptor 4 on dendritic cells, thereby stimulating optimal antigen processing. Cell death accompanied by autophagy also may facilitate cross priming events. Apoptosis, necrosis and autophagy are closely intertwined processes. Often, cells manifest autophagy before they undergo apoptosis or necrosis, and apoptosis is generally followed by secondary necrosis. Whereas apoptosis and necrosis irreversibly lead to cell death, autophagy can clear cells from stress factors and thus facilitate cellular survival. We surmise that the response to cellular stress like chemotherapy or ionizing irradiation, dictates the immunological response to dying cells and that this immune response in turn determines the clinical outcome of anticancer therapies. The purpose of this review is to summarize recent insights into the immunogenicity of dying tumor cells as a function of the cell death modality.


Cell death Calreticulin Cancer immunity 



G.K. is supported by a special grant from Ligue contre le Cancer (équipe labellisée) as well as by grants from European Commission (Active p53, AICR, RIGHT, Trans-Death, Death-Train, ChemoRes) and by Institut National contre le Cancer (INCa). O.K. receives a long term fellowship from EMBO, A.T is supported by INSERM. F.S. is supported by Fondation pour la recherché Medical, L.S. is supported by Death Train Network.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Oliver Kepp
    • 1
    • 2
    • 3
  • Antoine Tesniere
    • 1
    • 2
    • 3
  • Frederic Schlemmer
    • 1
    • 2
    • 3
  • Mickael Michaud
    • 1
    • 2
    • 3
  • Laura Senovilla
    • 1
    • 2
    • 3
  • Laurence Zitvogel
    • 2
    • 3
    • 4
    • 5
  • Guido Kroemer
    • 1
    • 2
    • 3
  1. 1.INSERM, U848VillejuifFrance
  2. 2.Institut Gustave RoussyVillejuifFrance
  3. 3.Université Paris-Sud 11VillejuifFrance
  4. 4.INSERM, U805VillejuifFrance
  5. 5.CIC BT507VillejuifFrance

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