Correlation between density of CD8 T cell infiltrates in microsatellite unstable colorectal cancers and frameshift mutations: a rationale for personalized immunotherapy Running title: CD8 cell density correlates with mutations in MSI-CRCs

نویسندگان

  • Pauline Maby
  • David Tougeron
  • Mohamad Hamieh
  • Bernhard Mlecnik
  • Hafid Kora
  • Gabriela Bindea
  • Helen K Angell
  • Tessa Fredriksen
  • Nicolas Elie
  • Emilie Fauquembergue
  • Aurélie Drouet
  • Jérôme Leprince
  • Jacques Benichou
  • Jacques Mauillon
  • Florence Le Pessot
  • Richard Sesboüé
  • Thierry Frébourg
  • Jérôme Galon
  • Jean-Baptiste Latouche
چکیده

4 Inserm U1138, Laboratory of Integrative Cancer Immunology, Paris, France; Université Paris Descartes, Paris, France; Cordeliers Research Centre, Université Pierre et Marie Curie, Paris 6, Paris, France; AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, UK Imaging Core Facility, CMABIO, Caen University Hospital, Caen, France; Inserm U982, Institute for Research and Innovation in Biomedecine (IRIB), Rouen

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منابع مشابه

Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy.

Colorectal cancers with microsatellite instability (MSI) represent 15% of all colorectal cancers, including Lynch syndrome as the most frequent hereditary form of this disease. Notably, MSI colorectal cancers have a higher density of tumor-infiltrating lymphocytes (TIL) than other colorectal cancers. This feature is thought to reflect the accumulation of frameshift mutations in sequences that a...

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Regulatory T Lymphocytes Are Associated with Less Aggressive Histologic Features in Microsatellite-Unstable Colorectal Cancers

BACKGROUND Colorectal cancers (CRCs) with microsatellite instability (MSI) are associated with a good prognosis and a high density of tumor-infiltrating lymphocytes (TILs). We have undertaken to determine the link between TIL densities and MSI CRC histologic features. PATIENTS AND METHODS Using tissue microarrays, T-cell sub-population infiltration, including T cells (CD3), cytotoxic T cells ...

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Mutational profiling of colorectal cancers with microsatellite instability

Microsatellite instability (MSI) is caused by defective mismatch repair in 15-20% of colorectal cancers (CRCs). Higher mutation loads in tumors with mismatch repair deficiency can predict response to pembrolizumab, an anti-programmed death 1 (PD-1) immune checkpoint inhibitor. We analyzed the mutations in 113 CRCs without MSI (MSS) and 29 CRCs with MSI-High (MSI-H) using the 50-gene AmpliSeq ca...

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Mutation and Expression of DNA2 Gene in Gastric and Colorectal Carcinomas

Background : Deregulation of DNA repair and replication are involved in cancer development. DNA2 is a nuclease/helicase that plays roles in DNA repair and replication. The aim of this study was to explore DNA2 mutation and DNA2 protein expression in gastric cancers (GCs) and colorectal cancers (CRCs). Methods : We analyzed two mononucleotide repeats in DNA2 in 27 GCs with high microsatellite in...

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The Different Roles of hRAD50 in Microsatellite Stable and Unstable Colorectal Cancers

RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138...

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تاریخ انتشار 2015