Oncotarget

Reviews:

Cross-talk between microbiota and immune fitness to steer and control response to anti PD-1/PDL-1 treatment

Andrea Botticelli, Ilaria Zizzari, Federica Mazzuca, Paolo Antonio Ascierto, Lorenza Putignani, Luca Marchetti, Chiara Napoletano, Marianna Nuti _ and Paolo Marchetti

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Oncotarget. 2017; 8:8890-8899. https://doi.org/10.18632/oncotarget.12985

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Abstract

Andrea Botticelli2,*, Ilaria Zizzari1,*, Federica Mazzuca2, Paolo Antonio Ascierto4, Lorenza Putignani3, Luca Marchetti5, Chiara Napoletano1, Marianna Nuti1,* and Paolo Marchetti2,*

1 Department of Experimental Medicine, “Sapienza University of Rome, Rome, Italy

2 Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, “Sapienza” University of Rome, Rome, Italy

3 Units of Parasitology and Human Microbiome, Bambino Gesù Children’s Hospital and Research Institute, Rome, Italy

4 Melanoma, Cancer Immunotherapy, and Innovative Therapy, Istituto nazionale Tumori Fondazione “G Pascale”, Napoli, Italy

5 Department of Clinical Oncology, Policlinico Umberto I, University of Rome Sapienza, Rome, Italy

Correspondence to:

Marianna Nuti, email:

* These authors have contributed equally to this work

Keywords: microbiome, immunotherapy, PD-1, PDL-1, CTLA-4

Received: July 18, 2016 Accepted: October 13, 2016 Published: October 28, 2016

Abstract

Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits. Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. Hence in the context of multiple treatment possibilities, the identification of predictive markers of response and toxicity is a challenging approach for drug selection in order to obtain the best clinical benefit while minimizing the side effects. The loss of the protective function of intestinal barriers that interacts with the environment measured as increased intestinal permeability and the changes occurring in the microbiota composition have been proposed as a mechanism potentially explaining the pathogenesis of immune related toxicity.

In this review we discuss the new perspectives on the involvement of PD-1 and PDL-1 in the cross talk between gut microbiota and immune fitness and how gut microbiota impacts on the efficacy of anti-PD-1 and anti-PDL-1 treatments in cancer.


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