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Immune parameters affecting the efficacy of chemotherapeutic regimens

Nature Reviews Clinical Oncology volume 8, pages 151–160 (2011)Cite this article

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Abstract

The outcome of chemotherapy can be influenced by the host immune system at multiple levels. Chemotherapy can kill cancer cells by causing them to elicit an immune response or alternatively, by increasing their susceptibility to immune attack. In addition, chemotherapy can stimulate anticancer immune effectors either in a direct fashion or by subverting immunosuppressive mechanisms. Beyond cancer-cell-intrinsic factors that determine the cytotoxic or cytostatic response, as well as the potential immunogenicity of tumor cells, the functional state of the host immune system has a major prognostic and predictive impact on the fate of cancer patients treated with conventional or targeted chemotherapies. In this Review, we surmise that immune-relevant biomarkers may guide personalized therapeutic interventions including compensatory measures to restore or improve anticancer immune responses.

Key Points

  • It is assumed that chemotherapy acts solely on tumor cells or has immunosuppressive side effects, thus excluding that the immune system may contribute to its therapeutic success

  • Signs of immune activation, and in particular specific anticancer immune response, after chemotherapy may predict therapeutic outcome in patients

  • The composition, function, architecture and gene-expression profile of the immune infiltrate of innate and cognate immune cells in tumors has a major impact on prognosis of most major cancers

  • The presence of CD45RO+ CD8+ memory effector T cells deep in the tumor parenchyma, as well as the local production and/or action of interferon-γ, has a positive prognostic impact

  • Loss-of-function alleles of the Toll-like receptor 4 and purinergic receptor P2RX7 are negative predictors of the response to adjuvant chemotherapy with anthracyclines or oxaliplatin

  • Optimal, personalized cancer therapy will rely on the evaluation of immunological biomarkers—both from the tumor and the immune system—and on compensatory measures that correct defects in the anticancer immune response

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Figure 1: Possible scenarios of chemotherapeutic action on the cancer–host relationship.
Figure 2: Dialog between dendritic cells and cancer cells that succumb to immunogenic cell death.
Figure 3: A hypothetical pathway involving the immune system in successful chemotherapy.

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Acknowledgements

G. Kroemer is supported by the Ligue Nationale contre le Cancer (Equipes labelisée), Agence Nationale pour la Recherche, European Commission (Active p53, Apo-Sys, ChemoRes, ApopTrain), Fondation pour la Recherche Médicale, Institut National du Cancer and Cancéropôle Ile-de-France.

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Authors and Affiliations

  1. INSERM U1015, Institut Gustave Roussy, 39 rue Camille Desmoulins, F-94805, Villejuif, France

    Laurence Zitvogel

  2. INSERM U848, Metabolomics Platform, Institut Gustave Roussy, 39 rue Camille Desmoulins, F-94805, Villejuif, France

    Oliver Kepp

  3. University of Paris Descartes, Faculty of Medicine, Centre de Recherche des Cordeliers, INSERM U872, 15 rue de l'Ecole de Médecine, F-75006, Paris, France

    Guido Kroemer

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L. Zitvogel, O. Kepp and G. Kroemer contributed equally to researching the data for the article, writing the article and to reviewing and/or editing of the manuscript before submission.

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Correspondence to Guido Kroemer.

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Zitvogel, L., Kepp, O. & Kroemer, G. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8, 151–160 (2011). https://doi.org/10.1038/nrclinonc.2010.223

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