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NKG2D is a Key Receptor for Recognition of Bladder Cancer Cells by IL-2-Activated NK Cells and BCG Promotes NK Cell Activation.

García-Cuesta EM, López-Cobo S, Álvarez-Maestro M, Esteso G, Romera-Cárdenas G, Rey M, Cassady-Cain RL, Linares A, Valés-Gómez A, Reyburn HT, Martínez-Piñeiro L, Valés-Gómez M - Front Immunol (2015)

Bottom Line: More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response.However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells.The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Oncology, National Centre for Biotechnology (CNB-CSIC) , Madrid , Spain.

ABSTRACT
Intravesical instillation of bacillus Calmette-Guérin (BCG) is used to treat superficial bladder cancer, either papillary tumors (after transurethral resection) or high-grade flat carcinomas (carcinoma in situ), reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory response, mediated by phagocytic uptake of mycobacterial antigens and cytokine release. More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response. Here, we provide a comprehensive study of multiple bladder cancer cell lines as putative targets for immune cells and evaluated their recognition by NK cells in the presence and absence of BCG. We describe that different bladder cancer cells can express multiple activating and inhibitory ligands for NK cells. Recognition of bladder cancer cells depended mainly on NKG2D, with a contribution from NKp46. Surprisingly, exposure to BCG did not affect the immune phenotype of bladder cells nor increased NK cell recognition of purified IL-2-activated cell lines. However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells. We also analyzed the percentage of NK cells in peripheral blood of a cohort of bladder cancer patients treated with BCG. The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.

No MeSH data available.


Related in: MedlinePlus

Expression of ligands for NK cells on bladder cancer cell lines. The indicated bladder cell lines were stained with antibodies specific for several NKG2D ligands (A), surface MHC, using the pan-MHC antibody HP1F7 (B) and the adhesion molecules E-cadherin and CD54 (C), and analyzed by flow cytometry. The figure shows a representative experiment out of more than five for each molecule. For more markers and statistical analysis, see Table 1 and Figure S1 in Supplementary Material.
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Figure 1: Expression of ligands for NK cells on bladder cancer cell lines. The indicated bladder cell lines were stained with antibodies specific for several NKG2D ligands (A), surface MHC, using the pan-MHC antibody HP1F7 (B) and the adhesion molecules E-cadherin and CD54 (C), and analyzed by flow cytometry. The figure shows a representative experiment out of more than five for each molecule. For more markers and statistical analysis, see Table 1 and Figure S1 in Supplementary Material.

Mentions: To characterize the ability of bladder cancer cells to stimulate NK cell responses, a panel of urothelial tumor cells with different grades of differentiation (T24, UM-UC-3, J82, RT-112, RT4, SW780) were stained with antibodies against different NK ligands for flow cytometry analysis. Three groups of molecules were checked: ligands for activating receptors, inhibitory ligands, and adhesion molecules involved in NK recognition. Figure 1 shows representative flow cytometry profiles and Figure S1 in Supplementary Material the statistical analysis of all the markers studied. For simplicity, FACS data and grade of tumor cell lines are summarized in Table 1. Notably, different urothelial cells show different patterns of immune ligands as well as MHC and adhesion molecules, suggesting that their susceptibility to NK cell lysis could be different.


NKG2D is a Key Receptor for Recognition of Bladder Cancer Cells by IL-2-Activated NK Cells and BCG Promotes NK Cell Activation.

García-Cuesta EM, López-Cobo S, Álvarez-Maestro M, Esteso G, Romera-Cárdenas G, Rey M, Cassady-Cain RL, Linares A, Valés-Gómez A, Reyburn HT, Martínez-Piñeiro L, Valés-Gómez M - Front Immunol (2015)

Expression of ligands for NK cells on bladder cancer cell lines. The indicated bladder cell lines were stained with antibodies specific for several NKG2D ligands (A), surface MHC, using the pan-MHC antibody HP1F7 (B) and the adhesion molecules E-cadherin and CD54 (C), and analyzed by flow cytometry. The figure shows a representative experiment out of more than five for each molecule. For more markers and statistical analysis, see Table 1 and Figure S1 in Supplementary Material.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4459093&req=5

Figure 1: Expression of ligands for NK cells on bladder cancer cell lines. The indicated bladder cell lines were stained with antibodies specific for several NKG2D ligands (A), surface MHC, using the pan-MHC antibody HP1F7 (B) and the adhesion molecules E-cadherin and CD54 (C), and analyzed by flow cytometry. The figure shows a representative experiment out of more than five for each molecule. For more markers and statistical analysis, see Table 1 and Figure S1 in Supplementary Material.
Mentions: To characterize the ability of bladder cancer cells to stimulate NK cell responses, a panel of urothelial tumor cells with different grades of differentiation (T24, UM-UC-3, J82, RT-112, RT4, SW780) were stained with antibodies against different NK ligands for flow cytometry analysis. Three groups of molecules were checked: ligands for activating receptors, inhibitory ligands, and adhesion molecules involved in NK recognition. Figure 1 shows representative flow cytometry profiles and Figure S1 in Supplementary Material the statistical analysis of all the markers studied. For simplicity, FACS data and grade of tumor cell lines are summarized in Table 1. Notably, different urothelial cells show different patterns of immune ligands as well as MHC and adhesion molecules, suggesting that their susceptibility to NK cell lysis could be different.

Bottom Line: More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response.However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells.The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Oncology, National Centre for Biotechnology (CNB-CSIC) , Madrid , Spain.

ABSTRACT
Intravesical instillation of bacillus Calmette-Guérin (BCG) is used to treat superficial bladder cancer, either papillary tumors (after transurethral resection) or high-grade flat carcinomas (carcinoma in situ), reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory response, mediated by phagocytic uptake of mycobacterial antigens and cytokine release. More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response. Here, we provide a comprehensive study of multiple bladder cancer cell lines as putative targets for immune cells and evaluated their recognition by NK cells in the presence and absence of BCG. We describe that different bladder cancer cells can express multiple activating and inhibitory ligands for NK cells. Recognition of bladder cancer cells depended mainly on NKG2D, with a contribution from NKp46. Surprisingly, exposure to BCG did not affect the immune phenotype of bladder cells nor increased NK cell recognition of purified IL-2-activated cell lines. However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells. We also analyzed the percentage of NK cells in peripheral blood of a cohort of bladder cancer patients treated with BCG. The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.

No MeSH data available.


Related in: MedlinePlus