Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance

Liu, Xiaowei; Song, Jing; Zhang, Hao; Liu, Xinyu; Zuo, Fengli; Zhao, Ying; Zhao, Yujie; Yin, Xiaomeng; Guo, Xinyu; Wu, Xi; Zhang, Hu; Xu, Jie; Hu, Jianping; Jing, Jing; Ma, Xuelei; Shi, Hubing

doi:10.1016/j.ccell.2023.01.001

Cited by 80 publications

(36 citation statements)

References 60 publications

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“…Platelets have been shown to facilitate metastasis by forming a “cloak” on the surface of the malignant cells, protecting them from NK cell-mediated cytotoxicity [ 12 , 15 , 25 , 26 ]. Indeed, we observed that in sensitive MM cells, platelets are capable of decreasing NK cell-mediated cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

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Sialofucosylation Enables Platelet Binding to Myeloma Cells via P-Selectin and Suppresses NK Cell-Mediated Cytotoxicity

Natoni

Cerreto

Propris

et al. 2023

Cancers

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Multiple myeloma (MM) is a plasma cell disorder that develops in the bone marrow (BM) and is characterized by uncontrolled proliferation and the ability to disseminate to different sites of the skeleton. Sialofucosylated structures, particularly Sialyl Lewis a/x (SLea/x), facilitate the homing of MM cells into the BM, leading to resistance to bortezomib in vivo. Platelets have been shown to play an important role in tumor metastasis. Platelets can bind to the surface of cancer cells, forming a “cloak” that protects them from the shear stress of the bloodstream and natural killer (NK) cell-mediated cytotoxicity. In this study, we showed that the presence of SLea/x induced a strong binding of MM cells to P-selectin, leading to specific and direct interactions with platelets, which could be inhibited by a P-selectin-blocking antibody. Importantly, platelets surrounded SLea/x-enriched MM cells, protecting them from NK cell-mediated cytotoxicity. The interactions between the platelets and MM cells were also detected in BM samples obtained from MM patients. Platelet binding to SLea/x-enriched MM cells was increased in patients with symptomatic disease and at relapse. These data suggest an important role of SLea/x and platelets in MM disease progression and resistance to therapy.

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Section: Discussionmentioning

confidence: 99%

“…Platelets participate in the metastatic cascade by different mechanisms [ 6 , 10 ]. In particular, it has been shown that activated platelets surround cancer cells, forming a “cloak” that protects malignant cells from the shear force caused by the blood flow [ 14 ] and from the immune attack of NK cells [ 12 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Sialofucosylation Enables Platelet Binding to Myeloma Cells via P-Selectin and Suppresses NK Cell-Mediated Cytotoxicity

Natoni

Cerreto

Propris

et al. 2023

Cancers

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“…So they would be trapped there before extravasating from blood and lymphatic vessels 97 , 98 ; 2) In the circulation system, these CTCs confront with a rather harsh habitat completely different from the original sites, where they are susceptible to anoikis and mechanical stress, and vulnerablely attacked by immune cells such as NK cells in the circulating 99 , 100 . The latest study demonstrates that platelet-derived RGS18 protects CTCs from NK-mediated immune surveillance by hijacking immune checkpoint HLA-E:CD94-NKG2A 101 ; 3) When cancer cells reach the distant sites, they have to adapt to the new microenvironment such as ECM components and the immune system seem to don't welcome their arrivals 102 . These disseminated tumor cells (DTCs) need to construct the local conditions as “ecological engineers” to set up their habitat to assist the survival 79 - 81 , 103 , that is, creating pre-metastatic niche (niche construction) such as immunosuppression, tumor-promoting inflammation, inducing angiogenesis and ECM reprogramming, and aerobic glycolysis producing an acidic local environment 104 - 106 .…”

Section: Npc As Invasive Species and Its Metastasis As An Ecological ...mentioning

confidence: 99%

Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem

Luo¹

2023

Theranostics

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Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer that is generally regarded as a genetic disease with diverse intertumor and intratumor heterogeneity. This perspective review mainly outlines the up-to-date knowledge of cancer ecology and NPC progression, and presents a number of conceptual stepping-stones. At the beginning, I explicitly advocate that the nature of NPC (cancer) is not a genetic disease but an ecological disease: a multidimensional spatiotemporal "unity of ecology and evolution" pathological ecosystem. The hallmarks of cancer is proposed to act as ecological factors of population fitness. Subsequently, NPC cells are described as invasive species and its metastasis as a multidirectional ecological dispersal. The foundational ecological principles include intraspecific relationship (e.g. communication) and interspecific relationship (e.g. competition, predation, parasitism and mutualism) are interpreted to understand NPC progression. "Mulberry-fish-ponds" model can well illustrate the dynamic reciprocity of cancer ecosystem. Tumor-host interface is the ecological transition zone of cancer, and tumor buddings should be recognized as ecological islands separated from the mainland. It should be noted that tumor-host interface has a significantly molecular and functional edge effect because of its curvature and irregularity. Selection driving factors and ecological therapy including hyperthermia for NPC patients, and future perspectives in such field as "ecological pathology", "multidimensional tumoriecology" are also discussed. I advance that "nothing in cancer evolution or ecology makes sense except in the light of the other". The cancer ecology tree is constructed to comprehensively point out the future research direction. Taken together, the establishment of NPC ecology theory and cancer ecology tree might provide a novel conceptual framework and paradigm for our understanding of cancer complex causal process and potential preventive and therapeutic applications for patients.

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“…They then confirmed metastatic tumor cell death related to DNAM-1 activation in NK cells [ 78 ]. Whereas a more recent study has shown that activation of inhibitory receptor NKG2A/HLA-E signaling promoted the distant metastasis of PDAC; blocking this pathway provokes NK cells and inhibits PDAC metastasis [ 127 ]. Whether the NK cells destroy metastatic cancer depends on the amounts of signals from activating and inhibitory receptors in the NK cells.…”

Section: The Function Of Nk Cells In Tumor Metastasismentioning

confidence: 99%

The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy

2023

Cancers

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Metastatic tumors cause the most deaths in cancer patients. Treating metastasis remains the primary goal of current cancer research. Although the immune system prevents and kills the tumor cells, the function of the immune system in metastatic cancer has been unappreciated for decades because tumors are able to develop complex signaling pathways to suppress immune responses, leading them to escape detection and elimination. Studies showed NK cell-based therapies have many advantages and promise for fighting metastatic cancers. We here review the function of the immune system in tumor progression, specifically focusing on the ability of NK cells in antimetastasis, how metastatic tumors escape the NK cell attack, as well as the recent development of effective antimetastatic immunotherapies.

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Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance

Cited by 80 publications

References 60 publications

Sialofucosylation Enables Platelet Binding to Myeloma Cells via P-Selectin and Suppresses NK Cell-Mediated Cytotoxicity

Sialofucosylation Enables Platelet Binding to Myeloma Cells via P-Selectin and Suppresses NK Cell-Mediated Cytotoxicity

Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem

The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy

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