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Therapy-induced microenvironmental changes in cancer

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Abstract

In the past decade, the focus of tumor biology research has been switching from the functional dissection of oncogenes and tumor suppressor genes to investigation of the cross-talk between tumor cells and their microenvironment. Tumorigenesis requires the organized assembly of cancer cells with non-malignant cells and non-cellular stroma, resembling an abnormal organogenesis. This process can be modulated by local cellular stress responses, such as senescence, ER stress and autophagy, and inflammatory and immunosuppressive cells and effector molecules within the tumor microenvironment (TME). Various cellular stress responses and cell death modalities are triggered in response to chemotherapies, radiotherapies, and targeted therapies (including immunotherapies). The exposure of immunostimulatory factors could (re)awaken anti-tumor immunity. Unexpectedly, the gut microbial flora is becoming recognized as an important external modulator of the TME. We will discuss in detail the TME changes that take place after certain cancer therapies, highlighting the importance of cellular stress responses, tumor-infiltrating immune cells, and microbiota-derived factors.

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Acknowledgments

Yuting MA is supported by the LabEx Immuno-Oncologie and Chinese National Thousand Talents Program and a research grant from Chinese Academy of Medical Sciences (CAMS) 2015RC310003. LZ and GK is supported by the Ligue contre le Cancer (équipes labelisées); Agence National de la Recherche (ANR)—Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Swiss Bridge Foundation, ISREC and the Paris Alliance of Cancer Research Institutes (PACRI). Heng YANG is supported by PACRI and CAMS grant 2015RC310003.

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Authors and Affiliations

  1. Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, 215123, China

    Yuting Ma & Heng Yang

  2. Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China

    Yuting Ma & Heng Yang

  3. Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, 75006, France

    Yuting Ma, Heng Yang & Guido Kroemer

  4. Université Paris Descartes, Sorbonne Paris Cité, Paris, 75006, France

    Yuting Ma, Heng Yang & Guido Kroemer

  5. Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 94800, Villejuif, France

    Jonathan M. Pitt, Guido Kroemer & Laurence Zitvogel

  6. INSERM U1015, 94800, Villejuif, France

    Jonathan M. Pitt & Laurence Zitvogel

  7. Université Paris Sud, Université Paris-Saclay, Faculté de Médecine, 94276, Le Kremlin Bicêtre, France

    Jonathan M. Pitt & Laurence Zitvogel

  8. Metabolomics and Cell Biology Platforms, Institut de Cancérologie Gustave Roussy Cancer Campus, Villejuif, 94805, France

    Guido Kroemer

  9. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, 75015, France

    Guido Kroemer

  10. Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, 17176, Sweden

    Guido Kroemer

  11. Center of Clinical Investigations in Biotherapies of Cancer (CICBT), 1428, Villejuif, 94805, France

    Laurence Zitvogel

  12. University of Paris Sud XI, Kremlin Bicêtre, France

    Laurence Zitvogel

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  1. Yuting Ma
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  2. Heng Yang
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  3. Jonathan M. Pitt
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  5. Laurence Zitvogel
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Ma, Y., Yang, H., Pitt, J.M. et al. Therapy-induced microenvironmental changes in cancer. J Mol Med 94, 497–508 (2016). https://doi.org/10.1007/s00109-016-1401-8

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