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The cancer-immune dialogue in the context of stress

Nature Reviews Immunology volume 24, pages 264–281 (2024)Cite this article

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Abstract

Although there is little direct evidence supporting that stress affects cancer incidence, it does influence the evolution, dissemination and therapeutic outcomes of neoplasia, as shown in human epidemiological analyses and mouse models. The experience of and response to physiological and psychological stressors can trigger neurological and endocrine alterations, which subsequently influence malignant (stem) cells, stromal cells and immune cells in the tumour microenvironment, as well as systemic factors in the tumour macroenvironment. Importantly, stress-induced neuroendocrine changes that can regulate immune responses have been gradually uncovered. Numerous stress-associated immunomodulatory molecules (SAIMs) can reshape natural or therapy-induced antitumour responses by engaging their corresponding receptors on immune cells. Moreover, stress can cause systemic or local metabolic reprogramming and change the composition of the gastrointestinal microbiota which can indirectly modulate antitumour immunity. Here, we explore the complex circuitries that link stress to perturbations in the cancer-immune dialogue and their implications for therapeutic approaches to cancer.

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Fig. 1: The effects of stress on cancer.
Fig. 2: The effect of glucocorticoids on the immune system and anticancer immune responses.
Fig. 3: The effect of catecholamines on the immune system and anticancer immune responses.
Fig. 4: The effect of other SAIMs on the immune system and anticancer immune responses.

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Acknowledgements

Y.M. is supported by Science and Technology Innovation 2030 Major Project (STI2030-Major Projects 2022ZD0205700), Natural Science Foundation of China (NSFC; grant No. 81972701), CAMS Innovation Fund for Medical Sciences (CIFMS; 2021-I2M-1-074, 2022-I2M-2-004), National special support plan for high-level talents, Suzhou Municipal Key Laboratory (SZS2023005) and Innovative and Entrepreneurial Team Program (Jiangsu Province). G.K. is supported by the Ligue contre le Cancer (équipe labellisée), Agence National de la Recherche (ANR)–Projets blancs, AMMICa US23/CNRS UMS3655, Association pour la recherche sur le cancer (ARC), Cancéropôle Ile-de-France, Fondation pour la Recherche Médicale (FRM), Equipex Onco-Pheno-Screen, European Joint Programme on Rare Diseases, the European Union Horizon 2020 Projects Oncobiome and Crimson, Institut National du Cancer (INCa), Institut Universitaire de France, LabEx Immuno-Oncology (ANR-18-IDEX-0001), High-end Foreign Expert Program in China (GDW20171100085), the RHU Immunolife, Seerave Foundation, SIRIC Stratified Oncology Cell DNA Repair and Tumour Immune Elimination (SOCRATE) and SIRIC Cancer Research and Personalized Medicine (CARPEM).

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  1. These authors contributed equally: Yuting Ma, Guido Kroemer.

Authors and Affiliations

  1. National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China

    Yuting Ma & Guido Kroemer

  2. Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, France

    Guido Kroemer

  3. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France

    Guido Kroemer

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

    Guido Kroemer

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

    Guido Kroemer

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All authors researched data for this Review. All authors contributed substantially to discussion of the content. Y.M. wrote and edited the manuscript before submission.

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Ma, Y., Kroemer, G. The cancer-immune dialogue in the context of stress. Nat Rev Immunol 24, 264–281 (2024). https://doi.org/10.1038/s41577-023-00949-8

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