A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
The different immune profiles of normal colonic mucosa in cancer-free Lynch syndrome carriers and Lynch syndrome colorectal cancer patients (2022)


Bohaumilitzky, L., Kluck, K., Hüneburg, R., Gallon, R., Nattermann, J., Kirchner, M., Kristiansen, G., Hommerding, O., Pfuderer, P. L., Wagner, L., Echterdiek, F., Kösegi, S., Müller, N., Fischer, K., Nelius, N., Hartog, B., Borthwick, G., Busch, E., Haag, G. M., . . . Ahadova, A. (2022). The different immune profiles of normal colonic mucosa in cancer-free Lynch syndrome carriers and Lynch syndrome colorectal cancer patients. Gastroenterology, 162(3), 907-919.e10. https://doi.org/10.1053/j.gastro.2021.11.029


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Bohaumilitzky, Lena; Kluck, Klaus; Hüneburg, Robert; Gallon, Richard; Nattermann, Jacob; Kirchner, Martina; Kristiansen, Glen; Hommerding, Oliver; Pfuderer, Pauline L.; Wagner, Lelia; et al.

Lehti tai sarja: Gastroenterology

ISSN: 0016-5085

eISSN: 1528-0012

Julkaisuvuosi: 2022

Volyymi: 162

Lehden numero: 3

Artikkelin sivunumerot: 907-919.e10

Kustantaja: Elsevier

Julkaisumaa: Yhdysvallat (USA)

Julkaisun kieli: englanti

DOI: https://doi.org/10.1053/j.gastro.2021.11.029

Linkki tutkimusaineistoon: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178516

Julkaisun avoin saatavuus: Ei avoin

Julkaisukanavan avoin saatavuus:


Tiivistelmä

Background and aims
Due 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.

Methods
CD3-positive, FOXP3-positive and CD8-positive T cells were quantified in 219, 233 and 201 formalin-fixed paraffin-embedded (FFPE) normal colonic mucosa tissue sections from CRC patients and LS cancer-free carriers and 26, 22 and 19 LS CRCs, respectively. CD3-positive T cells were also quantified in an independent cohort of 97 FFPE normal rectal mucosa tissue sections from LS carriers enrolled on the CAPP2 clinical trial. The expression of 770 immune-relevant genes was analyzed in a subset of samples using the NanoString nCounter platform.

Results
LS normal mucosa specimens showed significantly elevated CD3-, FOXP3- and CD8-positive T cell densities compared to non-LS controls. 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.

Conclusion
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.


YSO-asiasanat: syöpätaudit; paksusuolisyöpä; limakalvot; immuunivaste; Lynchin oireyhtymä

Vapaat asiasanat: colorectal cancer; normal mucosa; immune infiltration; tumor risk


Liittyvät organisaatiot


OKM-raportointi: Kyllä

Raportointivuosi: 2022

Alustava JUFO-taso: 3


Viimeisin päivitys 2022-19-08 klo 20:19