IL-18–Primed Helper NK Cells Collaborate with Dendritic Cells to Promote Recruitment of Effector CD8+ T Cells to the Tumor Microenvironment

Wong, Jeffrey L.; Berk, Erik; Edwards, Robert P.; Kaliński, Paweł

doi:10.1158/0008-5472.can-12-4366

Cited by 136 publications

(98 citation statements)

References 49 publications

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“…For example, IFN-g production by NK cells facilitates CD4 + T cell responses in the lymph node (LN) (2). Several findings highlight that NK cells promote the induction of CD8 + T cell-mediated immunity (3,4). Furthermore, NK cells enhance and rescue CD8 + T cell immunity in situations in which the CD4 + Th cell response is affected (5,6).…”

mentioning

confidence: 99%

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

Zheng¹,

Sun

Wei

et al. 2016

The Journal of Immunology

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Although recent clinical studies demonstrate that NK cell function is impaired in hepatitis B virus (HBV)–persistent patients, whether or how NK cells play a role in anti-HBV adaptive immunity remains to be explored. Using a mouse model mimicking acute HBV infection by hydrodynamic injection of an HBV plasmid, we observed that although serum hepatitis B surface Ag and hepatitis B envelope Ag were eliminated within 3 to 4 wk, HBV might persist for >8 wk in CD8−/− mice and that adoptive transfer of anti-HBV CD8+ T cells restored the ability to clear HBV in HBV-carrier Rag1−/− mice. These results indicate that CD8+ T cells are critical in HBV elimination. Furthermore, NK cells increased IFN-γ production after HBV plasmid injection, and NK cell depletion led to significantly increased HBV persistence along with reduced frequency of hepatitis B core Ag–specific CD8+ T cells. Adoptive transfer of IFN-γ–sufficient NK cells restored donor CD8+ T cell function, indicating that NK cells positively regulated CD8+ T cells via secreting IFN-γ. We also observed that NK cell depletion correlated with decreased effector memory CD8+ T cell frequencies. Importantly, adoptive transfer experiments showed that NK cells were involved in anti-HBV CD8+ T cell recall responses. Moreover, DX5+CD49a− conventional, but not DX5−CD49a+ liver-resident, NK cells were involved in improving CD8+ T cell responses against HBV. Overall, the current study reveals that NK cells, especially DX5+CD49a− conventional NK cells, promote the antiviral activity of CD8+ T cell responses via secreting IFN-γ in a mouse model mimicking acute HBV infection.

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mentioning

confidence: 99%

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

Zheng¹,

Sun

Wei

et al. 2016

The Journal of Immunology

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“…IL18 can convert NK cells into "helper" cells, which attract immature DCs via CCL3 and CCL4. CXCR3 and CCR5 ligands produced by DCs facilitate the recruitment of type I effector CD8 þ T cells against tumors (33). Conversely, studies by the Terme and colleagues show that IL18 suppresses the NK cell arm of tumor immunosurveillance in a PD-1-dependent manner by inducing Kit þ…”

Section: Discussionmentioning

confidence: 99%

TLR2 Limits Development of Hepatocellular Carcinoma by Reducing IL18-Mediated Immunosuppression

Sun

Chen

et al. 2015

Cancer Research

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“…Of note, NK cells are an effective treatment in human gastrointestinal cancer (45), and higher NKcell activity in human esophageal SCC is considered protective (31). IL12 and IL18 are associated with NK-cell activation and differentiation (46,47), whereas IL17A has been linked to increased NK-cell accumulation (31). All three of these markers were upregulated in the plasma by BRBs, ACs, and PCA at weeks 15 and 25, while the expression of IL12 was also significantly ÃÃ and ÃÃÃ significantly higher (P < 0.01 and 0.001, respectively) than rats treated with NMBA and fed control diet.…”

Section: Discussionmentioning

confidence: 99%

Dietary Consumption of Black Raspberries or Their Anthocyanin Constituents Alters Innate Immune Cell Trafficking in Esophageal Cancer

Peiffer

Wang

Zimmerman³

et al. 2016

Cancer Immunology Research

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Freeze-dried black raspberries (BRB), their component anthocyanins (AC), and a metabolite of BRB ACs, protocatechuic acid (PCA), inhibit the development of esophageal cancer in rats induced by the carcinogen, N-nitrosomethylbenzylamine (NMBA). All three components reduce inflammation in the esophagus and in plasma. The present study determined the relation of changes in inflammatory markers to infiltration of innate immune cells into NMBA-treated esophagus. Rats were injected with NMBA (0.35 mg/kg) for 5 weeks while on control diet. Following NMBA treatment, rats were fed diets containing 6.1% BRB powder, an AC-rich fraction of BRBs (3.8 mmol/g), or 500 ppm PCA. At weeks 15, 25, and 35, inflammatory biomarker expression in the plasma and esophagus was quantified, and infiltration of immune cells in the esophagus was examined. At all three time points, BRB, AC, and PCA similarly affected cytokine production in the esophagus and plasma of NMBA-treated rats, relative to the NMBA-only control. These included decreased expression of the proinflammatory cytokine IL1b and increased expression of the anti-inflammatory cytokine IL10. Moreover, all three diets also increased the expression of IL12, a cytokine that activates both cytolytic natural killer and CD8 þ T cells. In addition, the three diets also decreased infiltration of both macrophages and neutrophils into the esophagus. Overall, our results suggest that another mechanism by which BRBs, ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis is by altering cytokine expression and innate immune cell trafficking into tumor tissues.

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IL-18–Primed Helper NK Cells Collaborate with Dendritic Cells to Promote Recruitment of Effector CD8+ T Cells to the Tumor Microenvironment

Cited by 136 publications

References 49 publications

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

NK Cells Help Induce Anti–Hepatitis B Virus CD8+ T Cell Immunity in Mice

TLR2 Limits Development of Hepatocellular Carcinoma by Reducing IL18-Mediated Immunosuppression

Dietary Consumption of Black Raspberries or Their Anthocyanin Constituents Alters Innate Immune Cell Trafficking in Esophageal Cancer

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