Tumor-Associated Monocytes/Macrophages Impair NK-Cell Function via TGFβ1 in Human Gastric Cancer

Abstract

Natural killer (NK) cells are a major component of the host antitumor immune response in human cancer. However, the nature, functional regulation, and clinical relevance of NK cells in gastric cancer remain largely unknown. In this study, we showed that the percentages of NK cells in tumors were significantly decreased, and low percentages of tumor-infiltrating NK cells were positively correlated with poor survival and disease progression. Although the expression of activating and inhibitory receptors on NK cells was shown to be not different between tumor and nontumor tissues, NK cells in tumors had impaired effector functions, characterized by decreased IFNγ, TNFα, and Ki-67 expression. We found that tumor-infiltrating monocytes/macrophages were physically close to NK cells, and their percentages negatively correlated with IFNγ and TNFα NK-cell percentages. study showed that isolated tumor-associated monocytes/macrophages could impair NK-cell expression of IFNγ, TNFα, and Ki-67. Blockade of TGFβ1 attenuated such monocytes/macrophages-mediated impairment of NK-cell function. Our data suggest that human NK-cell function was impaired by tumor-associated monocytes/macrophages, and that restoring NK-cell function may be an important therapeutic strategy to prevent tumor immune escape in gastric cancer. .

NK Cell Exhaustion

“…For example, in human gastric cancers, tumor-infiltrating monocytes/macrophages were physically close to NK cells, and their percentages were negatively correlated with the percentages of IFN-γ + and TNF-α + cells among NK cells (16), indicating that these tumor-infiltrating monocytes/macrophages are associated with NK cell exhaustion. Such monocytes/macrophages could impair expression of IFN-γ, TNF-α, and Ki-67 in NK cells in a TGF-β-dependent manner in vitro (16), suggesting that these monocytes/macrophages might contribute to the exhaustion of NK cells in tumors.…”

Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9

“…[47][48][49][50][51] The importance of migration and homing of NK cells to disease sites is critical to its success for cell-based immunotherapy upon adoptive infusion. [47][48][49][50][51] The importance of migration and homing of NK cells to disease sites is critical to its success for cell-based immunotherapy upon adoptive infusion.…”

“…Tumour infiltration of NK cells in cancer patients is associated with good prognosis in multiple tumours. [47][48][49][50][51] The importance of migration and homing of NK cells to disease sites is critical to its success for cell-based immunotherapy upon adoptive infusion. The enhancement of tumour-specific chemokine receptor expression on NK cells may benefit NK cell immunotherapy in this regard, where CRISPR/Cas9 technology is applicable.…”

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

“…AIEgens can also act as biosensors for the detection of cytokines. Inflammation or disease normally accompany with elevated concentrations of cytokines . As one of the cytokines, interferon‐γ produced mainly by T‐cells and natural killer cells is important for the diagnosis of tuberculosis and other diseases .…”

“…Inflammation or disease normally accompany with elevated concentrations of cytokines. 102 As one of the cytokines, interferon-γ produced mainly by T-cells and natural killer cells is important for the diagnosis of tuberculosis and other diseases. 103 Figure 2) consisting of an oligonucleotide that had high specificity toward interferon-γ to detect trace levels of interferon-γ secreted by living cells.…”