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The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients

Bohaumilitzky, Lena ; Kluck, Klaus ; Hüneburg, Robert ; Gallon, Richard ; Nattermann, Jacob ; Kirchner, Martina ; Kristiansen, Glen ; Hommerding, Oliver ; Pfuderer, Pauline L. ; Wagner, Lelia ; Echterdiek, Fabian ; Kösegi, Svenja ; Müller, Nico ; Fischer, Konstantin ; Nelius, Nina ; Hartog, Ben ; Borthwick, Gillian ; Busch, Elena ; Haag, Georg Martin ; Bläker, Hendrik ; Möslein, Gabriela ; von Knebel Doeberitz, Magnus ; Seppälä, Toni T. ; Ahtiainen, Maarit ; Mecklin, Jukka-Pekka ; Bishop, D. Timothy ; Burn, John ; Stenzinger, Albrecht ; Budczies, Jan ; Kloor, Matthias ; Ahadova, Aysel

Gastroenterology (New York, N.Y. 1943), 2022-03, Vol.162 (3), p.907-919.e10 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients
Autor: Bohaumilitzky, Lena ; Kluck, Klaus ; Hüneburg, Robert ; Gallon, Richard ; Nattermann, Jacob ; Kirchner, Martina ; Kristiansen, Glen ; Hommerding, Oliver ; Pfuderer, Pauline L. ; Wagner, Lelia ; Echterdiek, Fabian ; Kösegi, Svenja ; Müller, Nico ; Fischer, Konstantin ; Nelius, Nina ; Hartog, Ben ; Borthwick, Gillian ; Busch, Elena ; Haag, Georg Martin ; Bläker, Hendrik ; Möslein, Gabriela ; von Knebel Doeberitz, Magnus ; Seppälä, Toni T. ; Ahtiainen, Maarit ; Mecklin, Jukka-Pekka ; Bishop, D. Timothy ; Burn, John ; Stenzinger, Albrecht ; Budczies, Jan ; Kloor, Matthias ; Ahadova, Aysel
Assuntos: Adult ; Aged ; Aged, 80 and over ; Carcinoma - genetics ; Carcinoma - immunology ; Carcinoma - pathology ; CD3 Complex - metabolism ; CD8-Positive T-Lymphocytes - pathology ; Colon - immunology ; Colorectal Cancer ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - immunology ; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology ; DNA-Binding Proteins - genetics ; Female ; Forkhead Transcription Factors - metabolism ; Heterozygote ; Humans ; Immune Infiltration ; Intestinal Mucosa - immunology ; Intestinal Mucosa - pathology ; Lymphocyte Count ; Lynch Syndrome ; Male ; Microsatellite Instability ; Middle Aged ; Mismatch Repair Endonuclease PMS2 - genetics ; MutL Protein Homolog 1 - genetics ; MutS Homolog 2 Protein - genetics ; Normal Mucosa ; Rectum - immunology ; T-Lymphocytes - metabolism ; T-Lymphocytes - pathology ; T-Lymphocytes, Regulatory - metabolism ; T-Lymphocytes, Regulatory - pathology ; Transcriptome ; Tumor Risk ; Young Adult
É parte de: Gastroenterology (New York, N.Y. 1943), 2022-03, Vol.162 (3), p.907-919.e10
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Owing to the high load of immunogenic frameshift neoantigens, tumors arising in individuals with Lynch syndrome (LS), the most common inherited colorectal cancer (CRC) syndrome, are characterized by a pronounced immune infiltration. However, the immune status of normal colorectal mucosa in LS is not well characterized. We assessed the immune infiltrate in tumor-distant normal colorectal mucosa from LS CRC patients, sporadic microsatellite-unstable (MSI) and microsatellite-stable (MSS) CRC patients, and cancer-free LS carriers. CD3-positive, FOXP3-positive, and CD8-positive T cells were quantified in, respectively, 219, 233, and 201 formalin-fixed paraffin-embedded (FFPE) normal colonic mucosa tissue sections from CRC patients and cancer-free LS carriers and 26, 22, and 19 LS CRCs. CD3-positive T cells were also quantified in an independent cohort of 97 FFPE normal rectal mucosa tissue sections from LS carriers enrolled in the CAPP2 clinical trial. The expression of 770 immune-relevant genes was analyzed in a subset of samples with the use of the NanoString nCounter platform. LS normal mucosa specimens showed significantly elevated CD3-, FOXP3-, and CD8-positive T-cell densities compared with non-LS control specimens. Gene expression profiling and cluster analysis revealed distinct immune profiles in LS carrier mucosa with and without cancer manifestation. Long-term follow-up of LS carriers within the CAPP2 trial found a correlation between mucosal T-cell infiltrate and time to subsequent tumor occurrence. LS carriers show elevated mucosal T-cell infiltration even in the absence of cancer. The normal mucosa immune profile may be a temporary or permanent tumor risk modifier in LS carriers. [Display omitted] Immune differences in the normal colonic mucosa of Lynch syndrome patients with colorectal cancer and cancer-free carriers suggest a possible tumor risk-modifying role of the local immune milieu in Lynch syndrome.
Editor: United States: Elsevier Inc
Idioma: Inglês

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The Different Immune Profiles of Normal Colonic Mucosa in Cancer-Free Lynch Syndrome Carriers and Lynch Syndrome Colorectal Cancer Patients

United States: Elsevier Inc

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