Expression of NK cell receptor ligands in primary colorectal cancer tissue in relation to the phenotype of circulating NK- and NKT cells, and clinical outcome.

Natural killer (NK) cells and natural killer T (NKT) cells are implicated in the development and progression of colorectal cancer (CRC). Tumor cells express NK cell receptor ligands that modulate their function. This study aimed to investigate the expression of such ligands in CRC in relation to the phenotype of circulating NK- and NKT cells, and clinical outcome. Primary tumor tissues were analyzed for protein expression of NK cell ligands using immunohistochemistry with automated image analysis in a cohort of 78 CRC patients. For 24 of the 78 patients, RNA expression of NK cell ligands was analyzed in primary tumor tissue using RNA sequencing. Receptor expression on circulating NK- and NKT cells was previously measured by us in 71 of the 78 patients using flow cytometry. High Proliferating Cell Nuclear Antigen (PCNA) protein expression in the primary tumor associated with shorter disease-free survival (DFS) of CRC patients (P = 0.026). A trend was observed towards shorter DFS in CRC patients with above-median galectin-3 protein expression in the primary tumor (P = 0.055). High protein expression of galectin-3, CD1d, and human leukocyte antigen (HLA) class I, and high RNA expression of UL16-binding protein (ULBP)-1, -2, and -5, and HLA-E in the tumor tissue correlated with low expression of the corresponding receptors on circulating NK- or NKT cells (P < 0.05). Galectin-3 and PCNA expression in the primary tumor may be prognostic biomarkers in CRC patients. Furthermore, our results suggest that NK cell receptor ligands expressed by tumor cells may modulate the phenotype of circulating NK- and NKT cells, and facilitate immune escape of metastasizing cells.

Krijgsman D ，Roelands J ，Andersen MN ，Wieringa CHLA ，Tollenaar RAEM ，Hendrickx W ，Bedognetti D ，Hokland M ，Kuppen PJK ... -  《-》

Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile.

Krijgsman D ，de Vries NL ，Skovbo A ，Andersen MN ，Swets M ，Bastiaannet E ，Vahrmeijer AL ，van de Velde CJH ，Heemskerk MHM ，Hokland M ，Kuppen PJK ... -  《-》

The Role of Adaptor Proteins in the Biology of Natural Killer T (NKT) Cells.

Gerth E ，Mattner J 《-》

Differential expression of natural killer activating and inhibitory receptors in patients with newly diagnosed systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) presents as the abnormal activation and over-proliferation of immune competent cells. Few studies have characterized the role of natural killer (NK) and NK T (NKT) cells in the pathogenesis of SLE, and therefore a consensus has not been reached as yet. Thirty-two patients with new-onset SLE and 15 healthy controls were recruited. Activated and inhibitory NK and NKT cells in peripheral blood were quantified by flow cytometry. The proportions of spontaneous and stimulated interferon (IFN)-γ(+) NK and NKT cells and CD107a(+) NK cells was examined. Finally, the potential relationship between the cell subsets and clinical indexes was analyzed. The proportions of NK and NKT cells (P = 0.002 and 0.004, respectively) as well as the proportions of NKG2C(+) NK cells, inhibitory NK and NKT cell subsets (P = 0.016, P = 0.019, P = 0.049, and P = 0.028, respectively) in SLE patients were significantly lower than those in controls. In contrast, the proportions of activated NK cells and NKT cell subsets were significantly higher (P = 0.036, P = 0.034, P = 0.005, and P = 0.007, respectively). Moreover, the proportions of stimulated IFN-γ(+) NKT cells were significantly higher than in the controls, and the proportions of stimulated CD107a(+) NKT cells in SLE patients were significantly lower than in the controls (P = 0.032 and P = 0.02, respectively). Lower proportions of NK and NKT cells, higher proportions of activated NK cells and activated NKT cells, lower proportions of inhibitory NK and NKT cells, higher NKT cell activity, and lower NKT cell degranulation may induce the autoimmune reaction involved in the pathogenesis of SLE.

Ye Z ，Ma N ，Zhao L ，Jiang ZY ，Jiang YF ... -  《-》

Preoperative Tim‑3 expression on peripheral NK cells is correlated with pathologic TNM staging in colorectal cancer.

Wang Y ，Sun J ，Gao W ，Song B ，Shao Q ，Zhao L ，Zhang Y ，Wang Q ，Zhang Y ，Qu X ... -  《-》