IL-6 Secretion by a Rat T9 Glioma Clone Induces a Neutrophil-Dependent Antitumor Response with Resultant Cellular, Antiglioma Immunity

Gräf, Martin; Prins, Robert M.; Merchant, Randall E.

doi:10.4049/jimmunol.166.1.121

Cited by 42 publications

(30 citation statements)

References 32 publications

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“…Once exposed to inflammatory signals, activated neutrophils produce cytokines and chemokines that influence T-cell differentiation. In several models, neutrophils recruited after infection indeed produced IFN-γ, TNF-α, and IL-12 and induced Th1 polarization of antigen-specific T lymphocytes that influence T-cell immune responses (11,(32)(33)(34)(35). Those findings suggest that neutrophils influence both the "induction" phase, when alloantigen is recognized by the recipient immune system, and the "effector" phase, when specific T-cell proliferation is accelerated (29).…”

Section: Discussionmentioning

confidence: 87%

“…It was recently shown that the neutrophil itself can take up antigens and transcribe and express the genes encoding major histocompatibility complex (MHC) molecules as well as costimulatory molecules, thereby behaving as antigen presenting cells (9,10). Additionally, once neutrophils are exposed to inflammatory signals, activated neutrophils produce cytokines and chemokines to induce Th1 polarization of antigen-specific T lymphocytes that influence the T-cell immune response (11). These observations suggest a linkage between neutrophils and the development of acute cellular rejection.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of Neutrophil Migration Ameliorates Rat Lung Allograft Rejection

Hirayama

Shiraishi

Shirakusa

et al. 2006

Mol Med

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Chemokines activate and recruit specific leukocyte subpopulations. We sought to determine whether neutrophil migration, which can contribute to the development of ischemia-reperfusion injury, correlates with lung allograft rejection. Orthotopic left lung allotransplantation was performed from Brown Norway (donor) to Fisher 344 (recipient) rats. Because the role of activated neutrophils in the development of allograft rejection is believed to be biphasic, we used specific CXC receptor inhibition with antileukinate in 2 dosing regimens. Recipients were allocated into 4 groups; A (early administration) received 2 doses of antileukinate (10.0 mg/kg) intramuscularly 24 h before and immediately after transplantation; B (continuous administration) continuously received antileukinate intraperitoneally (10.0 mg/kg/day) for 7 days after surgery. Groups A or B were compared with individual controls that received PBS alone. The progression of rejection was assessed radiographically. Histologic evaluation of allograft rejection based on pathologic rejection grade, performed on day 7, demonstrated significantly lower histologic rejection in group B compared with the control group (2.1 ± 1.0 vs. 3.3 ± 0.5; P = 0.018), whereas there was no significant difference in group A compared with the control group. There were no significant differences between the aeration scores of groups A or B compared with their control groups. Our data suggest that neutrophils may play a promoting role in the development of allograft rejection, and blockage of neutrophil migration may suppress acute lung allograft rejection.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Prevention of Neutrophil Migration Ameliorates Rat Lung Allograft Rejection

Hirayama

Shiraishi

Shirakusa

et al. 2006

Mol Med

View full text Add to dashboard Cite

show abstract

“…Several recent studies have shown the presence of an immunosuppressive cell population in tumor-bearing hosts that is capable of promoting tumor angiogenesis and suppressing T-cell responses and also expresses Gr1 and CD11b molecules (9)(10)(11)(12). However, mouse tumors genetically modified to express various cytokines exhibited increased neutrophil infiltration into the tumor bed, which was followed by enhanced T-cell infiltration and subsequent tumor regression (13)(14)(15). Furthermore, depletion of neutrophils reduced the number of CD8 + T cells infiltrating the tumor and tumor regression was abrogated.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Enhancement of Antitumor Immunity Is Regulated by Neutrophils

et al. 2007

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Photodynamic therapy (PDT) is a Food and Drug Administration-approved local cancer treatment that can be curative of early disease and palliative in advanced disease. PDT of murine tumors results in regimen-dependent induction of an acute local inflammatory reaction, characterized in part by rapid neutrophil infiltration into the treated tumor bed. In this study, we show that a PDT regimen that induced a high level of neutrophilic infiltrate generated tumor-specific primary and memory CD8 + T-cell responses. In contrast, immune cells isolated from mice treated with a PDT regimen that induced little or no neutrophilic infiltrate exhibited minimal antitumor immunity. Mice defective in neutrophil homing to peripheral tissues (CXCR2 À/À mice) or mice depleted of neutrophils were unable to mount strong antitumor CD8 + T-cell responses following PDT. Neutrophils seemed to be directly affecting T-cell proliferation and/or survival rather than dendritic cell maturation or T-cell migration. These novel findings indicate that by augmenting T-cell proliferation and/or survival, tumor-infiltrating neutrophils play an essential role in establishment of antitumor immunity following PDT. Furthermore, our results may suggest a mechanism by which neutrophils might affect antitumor immunity following other inflammation-inducing cancer therapies. Our findings lay the foundation for the rational design of PDT regimens that lead to optimal enhancement of antitumor immunity in a clinical setting. Immune-enhancing PDT regimens may then be combined with treatments that result in optimal ablation of primary tumors, thus inhibiting growth of primary tumor and controlling disseminated disease. [Cancer Res 2007;67(21):10501-10]

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“…Neutrophils are fully equipped with a variety of granules, which contain proteases enabling them to deliver lethal interventions against invading microorganisms (4)(5)(6). In addition to mounting a robust host defense, the activation of neutrophils also significantly contributes to the pathology of various acute inflammatory injuries in infections, autoimmune diseases, tumors, and graft rejections (6)(7)(8)(9)(10). Thus, the means to properly control the functional activities of neutrophils is of central importance to mounting robust host defense responses while also avoiding tissue damage (11)(12)(13).…”

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confidence: 99%

Kinase AKT1 Negatively Controls Neutrophil Recruitment and Function in Mice

Liu

Wang

et al. 2013

The Journal of Immunology

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Neutrophils are critically involved in host defense and inflammatory injury. However, intrinsic signaling mechanisms controlling neutrophil recruitment and activities are poorly defined. In this article, we showed that protein kinase AKT1 (also known as PKBα) is the dominant isoform expressed in neutrophils and is downregulated upon bacterial infection and neutrophil activation. AKT1 deficiency resulted in severe disease progression accompanied by recruitment of neutrophils and enhanced bactericidal activity in the acute inflammatory lung injury (ALI) and the Staphylococcus aureus infection mouse models. Moreover, the depletion of neutrophils efficiently reversed the aggravated inflammatory response, but adoptive transfer of AKT1−/− neutrophils could potentiate the inflammatory immunity, indicating an intrinsic effect of the neutrophil in modulating inflammation in AKT1−/− mice. In the ALI model, the infiltration of neutrophils into the inflammatory site was associated with enhanced migration capacity, whereas inflammatory stimuli could promote neutrophil apoptosis. In accordance with these findings, neutralization of CXCR2 attenuated neutrophil infiltration and delayed the occurrence of inflammation. Finally, the enhanced bactericidal activity and inflammatory immunity of AKT-deficient neutrophils were mediated by a STAT1-dependent, but not a mammalian target of rapamycin–dependent, pathway. Thus, our findings indicated that the AKT1–STAT1 signaling axis negatively regulates neutrophil recruitment and activation in ALI and S. aureus infection in mice.

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IL-6 Secretion by a Rat T9 Glioma Clone Induces a Neutrophil-Dependent Antitumor Response with Resultant Cellular, Antiglioma Immunity

Cited by 42 publications

References 32 publications

Prevention of Neutrophil Migration Ameliorates Rat Lung Allograft Rejection

Prevention of Neutrophil Migration Ameliorates Rat Lung Allograft Rejection

Photodynamic Therapy Enhancement of Antitumor Immunity Is Regulated by Neutrophils

Kinase AKT1 Negatively Controls Neutrophil Recruitment and Function in Mice

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