Biology subjects

Fichtner-Feigl, S.

Publications and source records attributed to Fichtner-Feigl, S..

2 recordsLinked to original sources

bioRxiv2021

Proteome biology of primary colorectal carcinoma and corresponding liver metastases

Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.

cancer biology↗

bioRxiv2021

Adaptive subsets limit the anti-tumoral NK-cell activity in Hepatocellular Carcinoma

Background and AimsHepatocellular carcinoma (HCC) is a global health burden with increasing incidence, poor prognosis and limited therapeutic options. Natural killer (NK) cells exhibit potent anti-tumoral activity and therefore represent potential targets for immunotherapeutic approaches in HCC treatment. However, the human NK-cell repertoire is highly diverse including conventional and adaptive NK cells that differ in phenotype and effector function. Adaptive NK-cell frequencies are increased in association with HCMV (human cytomegalovirus) seropositivity that is also common in HCC patients. In this study, we aimed to gain a better understanding of the NK-cell repertoire and the associated anti-tumoral activity in HCC patients. MethodsIn-depth phenotypic and functional flow-cytometry analyses of the HCMV-associated NK cell-repertoire obtained from 57 HCC patients, 33 liver cirrhosis patients and 36 healthy donors (HD). ResultsFirst, adaptive subsets are present in all three cohorts with conserved characteristics in patients with liver cirrhosis and HCC. Second, adaptive NK cells can be isolated from HCC tissue however lack features of tissue-residency and thus probably represent circulating/infiltrating lymphocytes. Third, the anti-tumoral activity by adaptive NK cells is reduced compared to conventional NK-cell subsets, also in HCC. Lastly, frequencies of adaptive NK cells were increased in patients suffering from Hepatitis B virus-associated HCC providing a link between etiology and the NK-cell repertoire in HCC. ConclusionAdaptive NK cells limit the anti-tumoral activitity of NK cells in HCC, especially in association with HBV infection that is accompanied by an expansion of this NK cell subset. Lay summaryIn patients with liver cancer (HCC), a subset of natural killer cells, so called adaptive NK cells show a diminished anti-tumoral activity compared to other, called conventional NK cells. Adaptive NK cells are expanded in patients with HCC associated to Hepatitis B virus infection. Thus, presence of adaptive NK cells contributes to the immune escape in HCC.

immunology↗