Details

Autor(en) / Beteiligte

• Kroemer, Guido
• Zitvogel, Laurence
• Kepp, Oliver

Titel

Immune parameters affecting the efficacy of chemotherapeutic regimens

Ist Teil von

• Nature reviews. Clinical oncology, 2011-03, Vol.8 (3), p.151-160

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• In this Review, Zitvogel and colleagues discuss the impact of immune parameters on the efficacy of chemotherapeutic regimens. They suggest that immune-relevant biomarkers may guide personalized therapeutic interventions including compensatory measures to restore or improve anticancer immune responses. 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