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Franck Pagès1, Clémence Granier2, Amos Kirilovsky1

  • 1Service d'immunologie biologique, plateforme d'immunomonitoring, hôpital européen Georges-Pompidou, AP-HP, Paris, France; Centre de recherche des Cordeliers, INSERM, eq15, UMRS 1138, Paris, France.

Bulletin Du Cancer
|January 7, 2017
PubMed
Summary
This summary is machine-generated.

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Predictive biomarkers for cancer immunotherapy are crucial as treatments like anti-CTLA-4 and anti-PD-1 fail in most patients. Identifying reliable markers, potentially within tumors or through combined approaches, can improve treatment selection and outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Biomarker Discovery

Background:

  • Cancer immunotherapies targeting co-inhibitory receptors (anti-CTLA-4, anti-PD-1) show promise but have limited efficacy in 70-80% of patients.
  • High costs and adverse effects necessitate the development of predictive biomarkers to guide treatment decisions.

Purpose of the Study:

  • To review and identify potential predictive biomarkers for response to cancer immunotherapies.
  • To explore biomarkers in peripheral blood, tumor tissue, and the gut microbiota.

Main Methods:

  • Literature review focusing on studies investigating biomarkers associated with clinical response to ipilimumab (anti-CTLA-4) and anti-PD-1/PD-L1 therapies.
  • Analysis of biomarkers including soluble interleukin-2 receptor, T-cell populations (ICOS+ CD4-T, CD8-T), PD-L1 expression, tumor mutational load, and gut microbiota composition.
Keywords:
BiomarqueursCD8-T cellLymphocytes T CD8MarkerMicroenvironnementMutations et néoépitopesPD-L1Tumoral microenvironmenttumoral

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Main Results:

  • Peripheral blood markers like high soluble IL-2 receptor and absence of ICOS+ CD4-T induction may predict non-response to anti-CTLA-4 in melanoma.
  • PD-L1 expression in lung adenocarcinoma and melanoma correlates with improved response to anti-PD-1/PD-L1, though standardization is needed.
  • CD8-T cell tumor infiltration and high in situ mutational load are associated with better responses to both anti-PD-1 and anti-CTLA-4 therapies.
  • Gut microbiota composition plays a significant role in immunotherapy response, as shown in preclinical studies.

Conclusions:

  • No single universal biomarker has been identified; however, tumor-compartment markers and multi-marker combinations show potential for predicting immunotherapy response.
  • Further research and standardization of assays are required for clinical translation of these predictive biomarkers.