Cross-talk between microbiota and immune fitness to steer and control response to anti PD-1/PDL-1 treatment.
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.
Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.
Andrea
A
Botticelli
Department of Experimental Medicine, "Sapienza University of Rome, Rome, Italy.
Ilaria
I
Zizzari
Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.
Federica
F
Mazzuca
Melanoma, Cancer Immunotherapy, and Innovative Therapy, Istituto nazionale Tumori Fondazione "G Pascale", Napoli, Italy.
Paolo Antonio
PA
Ascierto
Units of Parasitology and Human Microbiome, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
Lorenza
L
Putignani
Department of Clinical Oncology, Policlinico Umberto I, University of Rome Sapienza, Rome, Italy.
Luca
L
Marchetti
Department of Experimental Medicine, "Sapienza University of Rome, Rome, Italy.
Chiara
C
Napoletano
Department of Experimental Medicine, "Sapienza University of Rome, Rome, Italy.
Marianna
M
Nuti
Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.
Paolo
P
Marchetti
D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
CTLA-4; PD-1; PDL-1; immunotherapy; microbiome