Expression levels of UL16 binding protein 1 and natural killer group 2 member D affect overall survival in patients with gastric cancer following gastrectomy

Kamei, Ryoji; Yoshimura, Kiyoshi; Yoshino, Shigefumi; Inoue, Masaiwa; Asao, Tetsuji; Fuse, Masanori; Wada, Satoshi; Kuramasu, Atsuo; Furuya-Kondo, Tomoko; Oga, Atsunori; Iizuka, Norio; Suzuki, Nobuaki; Maeda, Nobuyo; Watanabe, Yusaku; Matsukuma, Satoshi; Iida, Michihisa; Takeda, Shigeru; Ueno, Takayoshi; Yamamoto, Noboru; Fukagawa, Takeo; Katai, Hitoshi; Sasaki, Hiroki; Hazama, Shoichi; Oka, M.; Nagano, Hiroaki

doi:10.3892/ol.2017.7354

Cited by 15 publications

(16 citation statements)

References 17 publications

(22 reference statements)

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“…Expression of NKG2D ligands has been observed in human cancers arising from a variety of tissues. Variable expression of MICA, MICB, and ULBP1-3 ligands was observed in hematopoietic malignancies, including acute and chronic leukemias of lymphoid and myeloid origins ( 40 ), in addition to solid tumors such as neuroblastoma ( 41 ), colorectal ( 42 ), ovarian ( 43 ), cervical ( 44 ), breast ( 45 ), pancreatic ( 46 ), melanoma ( 47 – 49 ), and gastric cancers ( 50 ). One common feature is the heterogeneity in ligand expression between cancer types and individuals ( 42 , 45 , 47 , 51 ), which hinders the prognostic value of NKG2D ligands in clinical assessment.…”

Section: Nkg2d In Tumor Immunitymentioning

confidence: 99%

The Paradoxical Role of NKG2D in Cancer Immunity

et al. 2018

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The activating receptor NKG2D and its ligands are recognized as a potent immune axis that controls tumor growth and microbial infections. With regards to cancer surveillance, various studies have demonstrated the antitumor function mediated by NKG2D on natural killer cells and on conventional and unconventional T cells. The use of NKG2D-deficient mice established the importance of NKG2D in delaying tumor development in transgenic mouse models of cancer. However, we recently demonstrated an unexpected, flip side to this coin, the ability for NKG2D to contribute to tumor growth in a model of inflammation-driven liver cancer. With a focus on the liver, here, we review current knowledge of NKG2D-mediated tumor surveillance and discuss evidence supporting a dual role for NKG2D in cancer immunity. We postulate that in certain advanced cancers, expression of ligands for NKG2D can drive cancer progression rather than rejection. We propose that the nature of the microenvironment within and surrounding tumors impacts the outcome of NKG2D activation. In a form of autoimmune attack, NKG2D promotes tissue damage, mostly in the inflamed tissue adjacent to the tumor, facilitating tumor progression while being ineffective at rejecting transformed cells in the tumor bed.

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Section: Nkg2d In Tumor Immunitymentioning

confidence: 99%

The Paradoxical Role of NKG2D in Cancer Immunity

et al. 2018

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“…In the latter report, the critical γδ T cell subpopulation were Vδ1 + (rather than Vδ2 + ) T cells and Vδ1 + T cell counts as well as detectable/inducible ULBP3 expression both associated positively with disease control in CLL patients ( 47 ). Along the same lines, a recent study showed that ULBP1 and NKG2D expression associated (positively) with longer overall survival of gastric cancer patients ( 48 ). Thus, enhancement of NKG2D ligand expression, as achieved by bortezomib or temozolomide treatment of multiple myeloma ( 49 ) and glioblastoma multiforme ( 50 ) cells, respectively, may have important therapeutic potential, even if NKG2D ligand shedding may constitute an important immune evasion mechanism ( 51 ).…”

Section: Nkg2d-dependent Activation Of Human γδ T Cellsmentioning

confidence: 81%

Working in “NK Mode”: Natural Killer Group 2 Member D and Natural Cytotoxicity Receptors in Stress-Surveillance by γδ T Cells

Silva‐Santos

Strid

2018

Front. Immunol.

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Natural killer cell receptors (NKRs) are germline-encoded transmembrane proteins that regulate the activation and homeostasis of NK cells as well as other lymphocytes. For γδ T cells, NKRs play critical roles in discriminating stressed (transformed or infected) cells from their healthy counterparts, as proposed in the “lymphoid stress-surveillance” theory. Whereas the main physiologic role is seemingly fulfilled by natural killer group 2 member D, constitutively expressed by γδ T cells, enhancement of their therapeutic potential may rely on natural cytotoxicity receptors (NCRs), like NKp30 or NKp44, that can be induced selectively on human Vδ1+ T cells. Here, we review the contributions of NCRs, NKG2D, and their multiple ligands, to γδ T cell biology in mouse and human.

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“…NKG2D plays a pivotal role in NK-mediated recognition and killing of GC as well [ 132 ]. This could be expected considering NKG2D ligands expression on GC [ 133 ] and it is suggested also by a better overall survival (OS) in patients with higher levels of NKG2D expression compared to patients with lower/no expression of NKG2D in TILs [ 133 , 134 ]. On the other hand, tumor-infiltrating CD56 + T cells expressing NKG2D could also contribute to this favorable effect [ 133 ].…”

Section: Nkg2d Role In Pdac Crc and Gcmentioning

confidence: 99%

“…This could be expected considering NKG2D ligands expression on GC [ 133 ] and it is suggested also by a better overall survival (OS) in patients with higher levels of NKG2D expression compared to patients with lower/no expression of NKG2D in TILs [ 133 , 134 ]. On the other hand, tumor-infiltrating CD56 + T cells expressing NKG2D could also contribute to this favorable effect [ 133 ]. Notably, NK cells can also kill gastric CD133 + cancer stem cells via NKG2D, thus suggesting their possible role in controlling GC relapses/progression [ 135 ].…”

Section: Nkg2d Role In Pdac Crc and Gcmentioning

confidence: 99%

Role of the Main Non HLA-Specific Activating NK Receptors in Pancreatic, Colorectal and Gastric Tumors Surveillance

Ferretti

Carlomagno

Pesce

et al. 2020

Cancers

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Human NK cells can control tumor growth and metastatic spread thanks to their powerful cytolytic activity which relies on the expression of an array of activating receptors. Natural cytotoxicity receptors (NCRs) NKG2D and DNAM-1 are those non-HLA-specific activating NK receptors that are mainly involved in sensing tumor transformation by the recognition of different ligands, often stress-induced molecules, on the surface of cancer cells. Tumors display several mechanisms aimed at dampening/evading NK-mediated responses, a relevant fraction of which is based on the downregulation of the expression of activating receptors and/or their ligands. In this review, we summarize the role of the main non-HLA-specific activating NK receptors, NCRs, NKG2D and DNAM-1, in controlling tumor growth and metastatic spread in solid malignancies affecting the gastrointestinal tract with high incidence in the world population, i.e., pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and gastric cancer (GC), also describing the phenotypic and functional alterations induced on NK cells by their tumor microenvironment.

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Expression levels of UL16 binding protein 1 and natural killer group 2 member D affect overall survival in patients with gastric cancer following gastrectomy

Cited by 15 publications

References 17 publications

The Paradoxical Role of NKG2D in Cancer Immunity

The Paradoxical Role of NKG2D in Cancer Immunity

Working in “NK Mode”: Natural Killer Group 2 Member D and Natural Cytotoxicity Receptors in Stress-Surveillance by γδ T Cells

Role of the Main Non HLA-Specific Activating NK Receptors in Pancreatic, Colorectal and Gastric Tumors Surveillance

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