Role of natural killer cells in lung cancer

Aktaş, Ozge Nur; Öztürk, Ayşe Bilge; Erman, Baran; Erus, Suat; Tanju, Serhan; Dilege, Şükrü

doi:10.1007/s00432-018-2635-3

Cited by 59 publications

(46 citation statements)

References 52 publications

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“…GM-CSF promotes inflammatory monocyte differentiation into DCs (41), which play critical roles in antigen presentation and T-cell priming (46). NK cells also play important roles in the antitumor immune response (47). By contrast, TANs inhibit an antitumor immune response (48), and decreased neutrophil levels support enhanced antitumor immune responses.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma

et al. 2020

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Despite substantial progress in lung cancer immunotherapy, the overall response rate in patients with KRAS-mutant lung adenocarcinoma (LUAD) remains low. Combining standard immunotherapy with adjuvant approaches that enhance adaptive immune responsessuch as epigenetic modulation of antitumor immunity-is therefore an attractive strategy. To identify epigenetic regulators of tumor immunity, we constructed an epigenetic-focused single guide RNA library and performed an in vivo CRISPR screen in a Kras G12D / Trp53 −/− LUAD model. Our data showed that loss of the histone chaperone Asf1a in tumor cells sensitizes tumors to anti-PD-1 treatment. Mechanistic studies revealed that tumor cell-intrinsic Asf1a defi ciency induced immunogenic macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression and potentiated T-cell activation in combination with anti-PD-1. Our results provide a rationale for a novel combination therapy consisting of ASF1A inhibition and anti-PD-1 immunotherapy. SIGNIFICANCE: Using an in vivo epigenetic CRISPR screen, we identifi ed Asf1a as a critical regulator of LUAD sensitivity to anti-PD-1 therapy. Asf1a defi ciency synergized with anti-PD-1 immunotherapy by promoting M1-like macrophage polarization and T-cell activation. Thus, we provide a new immunotherapeutic strategy for this subtype of patients with LUAD.

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Section: Discussionmentioning

confidence: 99%

In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma

et al. 2020

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“…Cytolytic enzymes and cytokines produced by NK cells, like IFN-γ, are beneficial to inhibit cancer cells [17] . The survival of lung cancer patients was closely related to the level of NK cells [18] , and patients' survival rates are bound up with the level of NK cells in primary squamous cell lung carcinoma [19] .…”

Section: Discussionmentioning

confidence: 99%

Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with sufentanil controlled analgesia — a randomized controlled trial.

Yun

Miao

et al. 2019

Preprint

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Background: Perioperative immune function plays an important role in the prognosis of patients.Several studies have indicated that low-dose opioid receptor blockers can improve immune function.Methods: Sixty-nine patients undergoing video-assisted thoracoscopic resection of the lung cancer were randomly assigned to either the naloxone group (n=35) or the non-naloxone group (n=34) for postoperative analgesia during the first 48 hours after the operation. Both groups received sufentanil and palonosetron via postoperative analgesia pump, while 0.05μg·kg-1·h-1 naloxone was added in naloxone group. The primary outcomes were the level of opioid growth factor OGF and immune function assessed by natural killer cells and CD4+/CD8+ T-cell ratio. Second outcomes were assessed by the intensity of postoperative pain, postoperative rescue analgesia dose, postoperative nausea and vomiting (PONV). Results: The level of OGF in the naloxone group increased significantly at 24 hours (p 0.001) and 48 hours after the operation (P<0.01). The natural killer cells (P<0.05) and CD4+/CD8+ T-cell ratio (P<0.01) in the naloxone group increased significantly at 48 hours after the operation. The rest VAS scores were better with naloxone at 12 and 24 hours after operation P<0.05 , and the coughing VAS scores were better with naloxone at 48 hours after the operation P<0.05). The consumption of postoperative rescue analgesics in the naloxone group was lower (0.00 0.00-0.00 vs 25.00 0.00-62.50 P<0.05). Postoperative nausea scores at 24 hours after operation decreased in naloxone group 0.00 (0.00-0.00) vs 1.00 (0.00-2.00), P < 0.01).Conclusion: Infusion of 0.05μg·kg-1·h-1 naloxone for patients undergoing sufentanil-controlled analgesia for postoperative pain can significantly increase the level of OGF, natural killer cells, and CD4+/CD8+ T-cell ratio compared with non-naloxone group and postoperative pain intensity, request for rescue analgesics, and opioid-related side effects can also be reduced. Trial registration: The trial was registered at the Chinese

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“…NK cells have been showed to play an important role in effective immune responses and immunosurveillance. class I molecules on virus-infected and cancer cells activates NK cells cytotoxicity and release of immunostimulatory cytokines like interferon gamma IFN-γ [17] . The survival of lung cancer patients was positively correlated with the degree of NK cells infiltration in lung cancer [18] .…”

Section: Discussionmentioning

confidence: 99%

Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with sufentanil controlled analgesia — a randomized controlled trial.

Yun

Miao

Yue

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Perioperative immune function plays an important role in the prognosis of patients. Several studies have indicated that low-dose opioid receptor blockers can improve immune function. Methods: Sixty-nine patients undergoing video-assisted thoracoscopic resection of the lung cancer were randomly assigned to either the naloxone group (n=35) or the non-naloxone group (n=34) for postoperative analgesia during the first 48 hours after the operation. Both groups received sufentanil and palonosetron via postoperative analgesia pump, while 0.05μg·kg-1·h-1 naloxone was added in naloxone group. The primary outcomes were the level of opioid growth factor（OGF）and immune function assessed by natural killer cells and CD4+/CD8+ T-cell ratio. Second outcomes were assessed by the intensity of postoperative pain, postoperative rescue analgesia dose, postoperative nausea and vomiting (PONV). Results: The level of OGF in the naloxone group increased significantly at 24 hours (p＜0.001) and 48 hours after the operation (P<0.01). The natural killer cells (P<0.05) and CD4+/CD8+ T-cell ratio (P<0.01) in the naloxone group increased significantly at 48 hours after the operation. The rest VAS scores were better with naloxone at 12 and 24 hours after operation（P<0.05）, and the coughing VAS scores were better with naloxone at 48 hours after the operation（P<0.05). The consumption of postoperative rescue analgesics in the naloxone group was lower (0.00（0.00-0.00）vs 25.00（0.00-62.50）），P<0.05). Postoperative nausea scores at 24 hours after operation decreased in naloxone group（0.00 (0.00-0.00) vs 1.00 (0.00-2.00), P < 0.01). Conclusion: Infusion of 0.05μg·kg-1·h-1 naloxone for patients undergoing sufentanil-controlled analgesia for postoperative pain can significantly increase the level of OGF, natural killer cells, and CD4+/CD8+ T-cell ratio compared with non-naloxone group，and postoperative pain intensity, request for rescue analgesics, and opioid-related side effects can also be reduced. Trial registration: ChiCTR1900021043 on January 26, 2019. Keywords: Low-dose naloxone, Opioid growth factor, Immune function, Postoperative pain, nausea, vomiting

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Role of natural killer cells in lung cancer

Abstract: The NK cell targeting strategy has not yet been approved for lung cancer treatment. More clinical studies focusing on the role of NK cells in lung cancer pathogenesis are warranted to develop novel NK cell-based therapeutic approaches for the treatment of lung cancer.

Cited by 59 publications

References 52 publications

In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma

In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma

Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with sufentanil controlled analgesia — a randomized controlled trial.

Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with sufentanil controlled analgesia — a randomized controlled trial.

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