Rat CD4+CD8+ Macrophages Kill Tumor Cells through an NKG2D- and Granzyme/Perforin-Dependent Mechanism

Baba, Tomohisa; Iwasaki, Shigeo; Maruoka, Takako; Suzuki, Akira; Tomaru, Utano; Ikeda, Hitoshi; Yoshiki, Takashi; Kasahara, Masanori; Ishizu, Akihiro

doi:10.4049/jimmunol.180.5.2999

Cited by 26 publications

(17 citation statements)

References 18 publications

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“…We found that approximately 91% of the CD45 pos cells were double positive for CD45 and F4/80 (a macrophage marker; Figure 2D, II), and approximately 16.1% of the population was double positive for CD45 and CD3 (T cell marker; Figure 2D, III). Of note, cells that express both macrophage and lymphoid markers have been described, which explains why we observed a small fraction of cells that are both F4/80 pos and CD3 pos (36).…”

Section: Assessing the Quality Of The Macs-based Protocolmentioning

confidence: 68%

Isolation of Epithelial, Endothelial, and Immune Cells from Lungs of Transgenic Mice with Oncogene-Induced Lung Adenocarcinomas

Bantikassegn

Song

Politi

2015

Am J Respir Cell Mol Biol

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Genetically engineered mouse models of lung adenocarcinoma have proven invaluable for understanding mechanisms of tumorigenesis, therapy response, and drug resistance. However, mechanistic studies focused on studying these processes in tumor-bearing mouse lungs are confounded by the fact that, in most cases, relevant signaling pathways are analyzed in whole-lung preparations, which are composed of a heterogeneous mixture of cells. Given our increasing knowledge about the roles played by different subpopulations of cells in the development of lung adenocarcinoma, separating the major cellular compartments of the tumor microenvironment is recommended to allow for a precise analysis of relevant pathways in each isolated cell type. In this study, we optimized magnetic-and fluorescence-based isolation protocols to segregate lung epithelial (CD326/epithelial cell adhesion molecule-positive), endothelial (CD31-positive), and immune (CD45-positive) cells, with high purity, from the lungs of transgenic mice with mutant epidermal growth factor receptor-induced lung adenocarcinomas. This approach, which can potentially be extended to additional lung adenocarcinoma models, enables delineation of the molecular features of individual cell types that can be used to gain insight into their roles in lung adenocarcinoma initiation, progression, and response to therapy.

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Section: Assessing the Quality Of The Macs-based Protocolmentioning

confidence: 68%

Isolation of Epithelial, Endothelial, and Immune Cells from Lungs of Transgenic Mice with Oncogene-Induced Lung Adenocarcinomas

Bantikassegn

Song

Politi

2015

Am J Respir Cell Mol Biol

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“…Whether the classical method by which macrophages enact ADCC (phagocytosis by the zipper mechanism 46,47 ) is available on the scale required remains to be determined. An observation of NK-type extracellular killing (utilizing granzymes and perforin) performed by a subset of rat macrophages has been recorded 48 but no similar reports have been found. Hubert et al 22 have described synapses formed in mice, during tumor rejection, between antibody-coated tumor cells and macrophages or neutrophils.…”

Section: What Is the Cytotoxic Mechanism Destroying Antibodycoated Cementioning

confidence: 98%

Three major uncertainties in the antibody therapy of cancer

Stevenson

2014

Haematologica

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Antibodies against surface molecules of human tumors are now frequently administered in combination with strong chemotherapy, increasing therapeutic efficacy but making the task of elucidating immunological events more difficult. Experiments on genetically manipulated mice indicate that antibody efficacy is greatest when IgG antibody coating tumor cells is engaged by the Fcγ-receptors of effector cells, chiefly the monocyte/macrophage lineage. Evidence suggests lesser roles for NK cells, neutrophils, receptor-mediated cytotoxicity and complement-mediated cytotoxicity. The classical mode of killing employed by macrophages is phagocytosis, but much has to be learned about optimally activating macrophages for this task, and about any other modes of cytotoxicity used. There is renewed interest in antigenic modulation, which implies removal of therapeutic antibody linked with antigen from target-cell surfaces. It is now apparent that this removal of immune complexes can be achieved either by internalization by the target cell, or by transfer of the complexes to another cell by trogocytosis. In trials, anti-idiotype antibodies surprisingly proved therapeutically more effective than anti-CD20, despite anti-idiotype being more effectively removed from target-cell surfaces by antigenic modulation. This anomalous result might reflect the fact that persistence of anti-CD20 immune complexes in large amounts induces serious effector modulation, which paralyzes macrophage attacks on antibody-coated cells. The case for effector modulation is argued by analogy with the therapeutic suppression of autoimmune inflammation by effector modulation, achieved by infusion either of normal IgG in large amounts, or of anti-red cell IgG in relatively small amounts. ABSTRACTexamined for tumor Id. Very low levels were detected in all patients, but they all subsequently remained in remission and this has been maintained up to the time of writing; a striking example of tumor dormancy.Anti-Id therapy is now in abeyance due to the logistical difficulties involved in preparing individual antibodies for each patient. However, follicular lymphomas have been found to present an unusual glycan on their variable domains, close to the idiotypic epitopes, so there is a prospect that, for these tumors, an antibody of good affinity aimed at the glycan could be an effective single substitute for multiple anti-Id preparations.

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“…Although further study is necessary to clarify how such molecular alteration was directly involved in a failure of C. trachomatis replication, such mutant cells are potentially useful for elucidating the interaction of pathogenic chlamydiae with lymphocytes. In addition, recent works using animals revealed that granzyme was expressed and produced not only in T cells or NK cells, but also in macrophages, although a counterpart in humans is yet to be discovered [41,42].…”

Section: Kubo T Et Almentioning

confidence: 99%

Chlamydia trachomatis serovar L2 infection model using human lymphoid Jurkat cells

Kubo

Ishida

Matsuo

et al. 2012

Microbial Pathogenesis

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Rat CD4+CD8+ Macrophages Kill Tumor Cells through an NKG2D- and Granzyme/Perforin-Dependent Mechanism

Cited by 26 publications

References 18 publications

Isolation of Epithelial, Endothelial, and Immune Cells from Lungs of Transgenic Mice with Oncogene-Induced Lung Adenocarcinomas

Isolation of Epithelial, Endothelial, and Immune Cells from Lungs of Transgenic Mice with Oncogene-Induced Lung Adenocarcinomas

Three major uncertainties in the antibody therapy of cancer

Chlamydia trachomatis serovar L2 infection model using human lymphoid Jurkat cells

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