Interleukin-2 activated microglia engulf tumor infiltrating T cells in the central nervous system

Tamakawa, Noriyuki; Saio, Masanao; Suwa, Tatsuhiko; Ohe, Naoyuki; Yoshimura, Shinichi; Iwama, Toru; Shinoda, Jun; Sakai, Noboru; Takami, Taro

doi:10.3892/ijmm.13.4.497

Cited by 3 publications

(7 citation statements)

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“…We further tried to deplete macrophages by anti-CD11b antibody administration because macrophage was the largest CD11b + cell population in the tumor environment (1,14,18). As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro

Ouyang

Saio²,

Suwa³

et al. 2006

Int J Oncol

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The contribution of tumor associated macrophage (TAM) to the induction of major histocompatibility complex (MHC) class I expression in vivo has not been reported precisely. In this study, we utilized Interleukin-2 (IL-2) cDNAintroduced B16 melanoma cells (B16/IL-2) and vehicle-alone control cells (B16/mock) to examine whether TAM could contribute to the induction of MHC class I on B16 cells in vivo. Interestingly, although B16/mock and B16/IL-2 did not express MHC class I in vitro, MHC class I was strongly expressed in vivo in B16/IL-2 in comparison to B16/mock. Although in vivo treatment of anti-NK1.1 antibody abolished MHC expression in B16/mock in vivo, the same treatment did not influence MHC expression in B16/IL-2. Interestingly, both anti-asialo GM1 and anti-CD11b treatment strongly decreased MHC expression in B16/IL-2. TAM expressed both asialo GM1 and CD11b antigen, and TAM recovered from B16/IL-2 produced interferon Á (IFNÁ) 6 times more than that from B16/mock. In addition, TAM recovered from B16/IL-2 secreted 33.64 times more IFNÁ in response to in vitro administration of IL-2. Therefore, we checked whether or not IL-2 could influence the expression of IL-2 receptors. TAM recovered from IL-2 expressed middle affinity receptor of IL-2 (CD122 and CD132) while that from B16/mock expressed low affinity receptor (CD25 and CD132). Finally, we observed that B16 cells became apoptotic with IFNÁ treatment in vitro. These results suggested that IL-2 augmented activation of TAM would play the main role in induction of the MHC class I molecule through secretion of IFNÁ, and would contribute to the IFNÁ-mediated apoptosis induction in tumor cells.

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Section: Discussionmentioning

confidence: 99%

“…In the tumor environment, tumor associated macrophage (TAM) is the largest population in number of immune cells (1) and is alternatively activated, causing tumor immunesuppression (2). For example, Interleukin-10 (IL-10) produced in TAM suppresses production of IL-12 (3).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro

Ouyang

Saio²,

Suwa³

et al. 2006

Int J Oncol

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“…After induction of anesthesia and exposure of the spleen through an abdominal incision, MC38/mock cells (1 × 10 6 cells) were injected intrasplenically on day 0. PC61 (0.1 mg) was administered intraperitoneally on days 7, 10, 13 and 16, and rIL-2 (5 × 10 4 IU) was administered daily by intraperitoneal injection on days [8][9][10][11][12][13][14][15][16]. PBS was administered instead of PC61 or rIL-2 as a vehicle control.…”

Section: Subcutaneous and Intrahepatic Implantation Of Tumor Cells Pmentioning

confidence: 99%

“…Establishment of the IL‐2 ‐transfected MC38 cell line was reported previously. ( 12 ) In brief, a mouse IL‐2 cDNA generated from splenocyte total RNA was amplified and inserted into pcDNA3.1/Hygro (Invitrogen). Purified plasmids and control vector (pcDNA3.1) were introduced into MC38 cells, and stable transfectants (MC38/IL‐2 and MC38/mock cells) were obtained.…”

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confidence: 99%

“…Cells were prepared as described elsewhere. ( 12 ) Collected tumors were minced and digested, and total cells in tumor suspension were stained with Via‐Probe, APC‐labeled anti‐CD3e, and PE‐labeled anti‐CD4, anti‐CD8b.2 or anti‐NK‐1.1, and the percentage of CD4 + CD3 + , CD8 + CD3 + or NK‐1.1 + CD3 − cells was analyzed by flow cytometry. To examine the characteristics of TIL, these cells were isolated from the tumor cell suspension using MACS separation columns (Miltenyi Biotec, Bergisch Gladbach, Germany) after incubation with CD4 or CD8a MicroBeads (Miltenyi Biotec).…”

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Depletion of CD4⁺CD25⁺ regulatory T cells enhances interleukin‐2‐induced antitumor immunity in a mouse model of colon adenocarcinoma

Imai¹,

Saio²,

Nonaka³

et al. 2007

Cancer Science

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T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4+ and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/ mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 ± ± ± ± 0.03 g, less than that in mice treated with rIL-2 (2.04 ± ± ± ± 0.51 g) or PC61 alone (1.81 ± ± ± ± 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8 + T-cell population. (Cancer Sci 2007; 98: [416][417][418][419][420][421][422][423]

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Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

Shevchuk

Radoja²

2007

Infect Agents Cancer

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BackgroundThe phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. In particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. This type of regimen (for 8 days) has been shown to improve survival of mice infected with intracellular parasite Toxoplasma gondii, which would also be consistent with enhanced cell-mediated immunity.Presentation of the hypothesisThis paper hypothesizes that brief cold-water stress repeated daily over many months could enhance anti-tumor immunity and improve survival rate of a non-lymphoid cancer. The possible mechanism of the non-specific stimulation of cellular immunity by repeated cold stress appears to involve transient activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as described in more detail in the text. Daily moderate cold hydrotherapy is known to reduce pain and does not appear to have noticeable adverse effects on normal test subjects, although some studies have shown that it can cause transient arrhythmias in patients with heart problems and can also inhibit humoral immunity. Sudden immersion in ice-cold water can cause transient pulmonary edema and increase permeability of the blood-brain barrier, thereby increasing mortality of neurovirulent infections.Testing the hypothesisThe proposed procedure is an adapted cold swim (5–7 minutes at 20 degrees Celsius, includes gradual adaptation) to be tested on a mouse tumor model. Mortality, tumor size, and measurements of cellular immunity (numbers and activity of peripheral CD8+ T lymphocytes and natural killer cells) of the cold-exposed group would be compared to those of control groups (warm swim and no treatment). Cold-water stress would be administered twice a day for the duration of several months.Implications of the hypothesisIf the hypothesis is supported by empirical studies and the method is shown to be safe, this could lead to the development of an adjunctive immunotherapy for some (non-lymphoid) cancers, including those caused by viral infections.

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Interleukin-2 activated microglia engulf tumor infiltrating T cells in the central nervous system

Cited by 3 publications

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Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro

Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro

Depletion of CD4⁺CD25⁺ regulatory T cells enhances interleukin‐2‐induced antitumor immunity in a mouse model of colon adenocarcinoma

Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

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Interleukin-2 activated microglia engulf tumor infiltrating T cells in the central nervous system

Cited by 3 publications

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Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro

Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro

Depletion of CD4+CD25+ regulatory T cells enhances interleukin‐2‐induced antitumor immunity in a mouse model of colon adenocarcinoma

Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

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Depletion of CD4⁺CD25⁺ regulatory T cells enhances interleukin‐2‐induced antitumor immunity in a mouse model of colon adenocarcinoma