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. 2023 Jul;43(7):855-859.
doi: 10.1002/cac2.12446. Epub 2023 Jun 14.

Renal cell carcinoma escapes NK cell-mediated immune surveillance through the downregulation of DNAM-1

Le Tong  1 , Veronika Kremer  1 , Shi Yong Neo  1   2 , Yaxuan Liu  1 , Yi Chen  1   3 , Arnika Kathleen Wagner  4 , Ying Yang  1 , Ziqing Chen  1   5 , Christina Seitz  6 , Nicholas Patrick Tobin  1 , Maarten Alexander Ligtenberg  1   7 , Evren Alici  4 , Xinsong Chen  1 , Felix Haglund  1 , Barbara Seliger  8   9 , Ulrika Harmenberg  1 , Eugenia Colón  10 , Ann-Helén Scherman Plogell  11 , Lisa Lei Liu  1 , Andreas Lundqvist  1
Affiliations

Renal cell carcinoma escapes NK cell-mediated immune surveillance through the downregulation of DNAM-1

Le Tong et al. Cancer Commun (Lond). 2023 Jul.
No abstract available

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Conflict of interest statement

No competing interests are related to this work.

Figures

FIGURE 1
FIGURE 1
RCC tumors induce DNAM‐1 downregulation on NK cells and attenuate their activity via PVR. (A) Overall survival in RCC patients stratified by high and low DNAM‐1 or PVR expression. P values were calculated by log‐rank test. (B) Frequencies of DNAM‐1+ NK cells and mean fluorescence intensity (MFI) of NK cells in blood and tumor of RCC patients (n = 14 patients). (C) Inverse correlation of PVR expression on tumor tissue and frequencies of DNAM‐1+ NK cells in RCC tumor tissue (Spearman correlation) (n = 14 patients). (D) Frequencies of DNAM‐1+ NK cells after 2‐day co‐culture of NK cells and WT Caki‐1 or PVR‐KO Caki‐1 cells (n = 7 biological replicates). Data are depicted as mean ± SD. Fold change in the frequency of DNAM‐1+ NK cells between co‐culture with WT and PVR‐KO Caki‐1 is 6.5. (E) Specific killing of WT Caki‐1 target by tumor‐experienced NK cells (n = 4 biological replicates). Data are depicted as mean ± SD. (F) t‐distributed stochastic neighbor embedding (t‐SNE) of different NK cell clusters origin in PBMC and tumor. (G) GO and KEGG pathway enrichment of different NK clusters. (H) Expression of CBLB on NK cells from different clusters in PBMC and tumor. (I) Frequencies of DNAM‐1+ NK after co‐culture with Caki‐1 in the absence or presence of warfarin (n = 4 biological replicates). Abbreviations: RCC, renal cell carcinoma; DNAM‐1, DNAX accessory molecule‐1; NK, natural killer; PVR, poliovirus receptor; MFI, mean fluorescence intensity; WT, wild type; KO, knockout; eNK, experienced NK; t‐SNE, t‐distributed stochastic neighbor embedding; PBMC, peripheral blood mononuclear cell; GO, gene ontology; KEGG, Kyoto encyclopedia of genes and genomes; CBLB, Casitas B‐Lineage Lymphoma Proto‐Oncogene B.
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