We have explored MICA/B expression and its relationship with innate inflammatory infiltrate in renal cell carcinoma (RCC). The expression of MICA/B, CD16, CD56, and CD68 in 140 RCC lesions contained in a tissue microarray (TMA) was investigated by immunohistochemistry. MICA/B gene and protein expressions in Caki-1 cells were analyzed by reverse transcription-polymerase chain reaction and flow cytometry, respectively. Natural killer (NK) cells were studied by flow cytometry. All the RCC lesions (n = 140) were MICA/B-positive. MICA/B was mainly expressed in the cytoplasm of tumor cells, whereas stromal cells were negative. Renal cell carcinoma lesions showed low NK cell infiltration, although they were rich in CD16+CD56- cells, strongly resembling macrophages. CD16+ macrophage infiltration was more frequently detectable in metastatic lesions compared with primary tumors (P = .0223) and was associated with poor RCC differentiation (P = .007). To investigate mechanisms potentially underlying the lack of NK cells infiltration into MICA/B-positive RCC lesions, we used Caki-1 RCC cells. Caki-1 expressed MICA and MICB genes. However, MICA protein was not detectable in Caki-1 cells, whereas MICB protein was detectable in their cytoplasm and on the cell membrane. Coculture of peripheral blood mononuclear cells with Caki-1, K562, HCT116, respectively, resulted in CD56+CD16+ NK cells deletion without affecting CD56+/CD16- NK subset and immature NK cells generated in vitro from CD34+ cells. Natural killer cell apoptosis seemed to be preferentially triggered by cancer cells because HLA-A0201+ NK cells were only marginally affected by allogeneic HLA-A0201- peripheral blood mononuclear cells. Caki-1 cell-mediated NK cell apoptosis was reduced by an anti-β2-integrin (CD18) monoclonal antibody but was NKG2D-, granule exocytosis-, and caspase-independent. Copyright © 2009 Neoplasia Press, Inc. All rights reserved.
Sconocchia, G., Spagnoli, G., Del Principe, D., Ferrone, S., Anselmi, M., Wongsena, W., et al. (2009). Defective infiltration of natural killer cells in MICA/B-positive renal cell carcinoma involves β2-integrin-mediated interaction. NEOPLASIA, 11(7), 662-671 [10.1593/neo.09296].
Defective infiltration of natural killer cells in MICA/B-positive renal cell carcinoma involves β2-integrin-mediated interaction
CERVELLI, VALERIO;
2009-01-01
Abstract
We have explored MICA/B expression and its relationship with innate inflammatory infiltrate in renal cell carcinoma (RCC). The expression of MICA/B, CD16, CD56, and CD68 in 140 RCC lesions contained in a tissue microarray (TMA) was investigated by immunohistochemistry. MICA/B gene and protein expressions in Caki-1 cells were analyzed by reverse transcription-polymerase chain reaction and flow cytometry, respectively. Natural killer (NK) cells were studied by flow cytometry. All the RCC lesions (n = 140) were MICA/B-positive. MICA/B was mainly expressed in the cytoplasm of tumor cells, whereas stromal cells were negative. Renal cell carcinoma lesions showed low NK cell infiltration, although they were rich in CD16+CD56- cells, strongly resembling macrophages. CD16+ macrophage infiltration was more frequently detectable in metastatic lesions compared with primary tumors (P = .0223) and was associated with poor RCC differentiation (P = .007). To investigate mechanisms potentially underlying the lack of NK cells infiltration into MICA/B-positive RCC lesions, we used Caki-1 RCC cells. Caki-1 expressed MICA and MICB genes. However, MICA protein was not detectable in Caki-1 cells, whereas MICB protein was detectable in their cytoplasm and on the cell membrane. Coculture of peripheral blood mononuclear cells with Caki-1, K562, HCT116, respectively, resulted in CD56+CD16+ NK cells deletion without affecting CD56+/CD16- NK subset and immature NK cells generated in vitro from CD34+ cells. Natural killer cell apoptosis seemed to be preferentially triggered by cancer cells because HLA-A0201+ NK cells were only marginally affected by allogeneic HLA-A0201- peripheral blood mononuclear cells. Caki-1 cell-mediated NK cell apoptosis was reduced by an anti-β2-integrin (CD18) monoclonal antibody but was NKG2D-, granule exocytosis-, and caspase-independent. Copyright © 2009 Neoplasia Press, Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
