title: Tumor genotype and immune microenvironment in POLE-ultramutated and MSI-hypermutated Endometrial Cancers: New candidates for checkpoint blockade immunotherapy?
abstract: Endometrial Cancer (EC) is still a challenge for gynecological oncologists because the treatment of the advanced disease remains an unmet need for patients. The Cancer Genome Atlas Research Network (TCGA) recently provided a comprehensive genomic and transcriptomic analysis of EC, offering a new classification of the disease, based on genetic features, which defines four subgroups of cancer rather than the two traditionally recognized. In the molecular classification two types of EC, the polymerase epsilon (POLE)-ultramutated and the microsatellite instability (MSI)-hypermutated, seem to present an enhanced immune microenvironment and a high mutation burden. The blockade of the immune checkpoints is an innovative approach that has largely demonstrated to be effective in solid malignancies, such as lung, renal and melanoma; it acts by reducing the cancer-induced immune-suppression through inhibition of the PD-1/PD-L1 (Programmed Death and PD-Ligand) axis. All available evidence supporting an over-expression of the PD-1/PD-L1 pathway in EC has been reviewed. In particular in the POLE and MSI ECs an up-regulation of this pathway was found, aiming to suggest a rationale for testing the PD-1/PD-L1 immunotherapy in these cancer subgroups.
authors.affiliation: Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Effingerstrasse 33, CH-3008 Bern, Switzerland; Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: pieragargiulo@hotmail.it.
authors.forename: Piera
authors.initials: P
authors.lastname: Gargiulo
authors.affiliation: Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: chiaradellapepa@hotmail.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Della Pepa
authors.affiliation: Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Effingerstrasse 33, CH-3008 Bern, Switzerland. Electronic address: Simona.Berardi@sakk.ch.
authors.forename: Simona
authors.initials: S
authors.lastname: Berardi
authors.affiliation: Department of Research-Functional Genomics, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: d.califano@istitutotumori.na.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Califano
authors.affiliation: Department of Research-Functional Genomics, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: s.scala@istitutotumori.na.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
authors.affiliation: Molecular Biology and Viral Oncogenesis Unit, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: l.buonaguro@istitutotumori.na.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Buonaguro
authors.affiliation: Scientific Directorate, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: g.ciliberto@istitutotumori.na.it.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Effingerstrasse 33, CH-3008 Bern, Switzerland. Electronic address: peter.brauchli@sakk.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Brauchli
authors.affiliation: Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola 52, 80131 Naples, Italy. Electronic address: s.pignata@istitutotumori.na.it.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
mesh_terms: D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D004257:DNA Polymerase II / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053842:Microsatellite Instability; D000075223:Poly-ADP-Ribose Binding Proteins; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D061026:Programmed Cell Death 1 Receptor; D004257:DNA Polymerase II; C119525:POLE protein, human
keywords: Endometrial Cancer; Immunotherapy; MSI-hypermutated; PD-1/PD-L1 axis; POLE-ultramutated; Tumor Infiltrating Lymphocytes (TILs)