Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma
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Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma. / Rennert, Charlotte; Tauber, Catrin; Fehrenbach, Pia; Heim, Kathrin; Bettinger, Dominik; Sogukpinar, Özlem; Schuch, Anita; Zecher, Britta Franziska; Bengsch, Bertram; Lang, Sven A; Bronsert, Peter; Björkström, Niklas K; Fichtner-Feigl, Stefan; Schultheiss, Michael; Thimme, Robert; Hofmann, Maike.
In: CELLS-BASEL, Vol. 10, No. 6, 02.06.2021, p. 1369.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Adaptive Subsets Limit the Anti-Tumoral NK-Cell Activity in Hepatocellular Carcinoma
AU - Rennert, Charlotte
AU - Tauber, Catrin
AU - Fehrenbach, Pia
AU - Heim, Kathrin
AU - Bettinger, Dominik
AU - Sogukpinar, Özlem
AU - Schuch, Anita
AU - Zecher, Britta Franziska
AU - Bengsch, Bertram
AU - Lang, Sven A
AU - Bronsert, Peter
AU - Björkström, Niklas K
AU - Fichtner-Feigl, Stefan
AU - Schultheiss, Michael
AU - Thimme, Robert
AU - Hofmann, Maike
PY - 2021/6/2
Y1 - 2021/6/2
N2 - Hepatocellular 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 anti-tumoral activity of NK cells in HCC associated with different etiologies, and the impact of the heterogeneous NK cell subset, e.g., adaptive and conventional subsets, are not understood in detail. By comparatively analyzing the NK-cell repertoire in 60 HCC patients, 33 liver cirrhosis patients and 36 healthy donors (HD), we show in this study that the NK-cell repertoire is linked to HCC etiology, with increased frequencies of adaptive NK cells in Hepatitis B virus (HBV)-associated HCC. Adaptive NK cells exhibited limited anti-tumoral activity toward liver cancer cells; however, this was not a result of a specific NK-cell impairment in HCC but rather represented an intrinsic feature, since the characteristics of circulating and intra-tumoral adaptive NK cells were conserved between HD, HCC and liver cirrhosis patients. Hence, the expansion of adaptive NK cells with reduced anti-tumoral activity, detectable in HBV-associated HCC, may have implications for tumor surveillance and therapy.
AB - Hepatocellular 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 anti-tumoral activity of NK cells in HCC associated with different etiologies, and the impact of the heterogeneous NK cell subset, e.g., adaptive and conventional subsets, are not understood in detail. By comparatively analyzing the NK-cell repertoire in 60 HCC patients, 33 liver cirrhosis patients and 36 healthy donors (HD), we show in this study that the NK-cell repertoire is linked to HCC etiology, with increased frequencies of adaptive NK cells in Hepatitis B virus (HBV)-associated HCC. Adaptive NK cells exhibited limited anti-tumoral activity toward liver cancer cells; however, this was not a result of a specific NK-cell impairment in HCC but rather represented an intrinsic feature, since the characteristics of circulating and intra-tumoral adaptive NK cells were conserved between HD, HCC and liver cirrhosis patients. Hence, the expansion of adaptive NK cells with reduced anti-tumoral activity, detectable in HBV-associated HCC, may have implications for tumor surveillance and therapy.
U2 - https://doi.org/10.3390/cells10061369
DO - https://doi.org/10.3390/cells10061369
M3 - SCORING: Journal article
C2 - 34199483
VL - 10
SP - 1369
JO - CELLS-BASEL
JF - CELLS-BASEL
SN - 2073-4409
IS - 6
ER -