Alveolar macrophage function is altered in patients with lung cancer

Pouniotis, Dodie; Plebanski, Magdalena; Apostolopoulos, Vasso; McDonald, Christine F

doi:10.1111/j.1365-2249.2006.02998.x

Cited by 38 publications

(40 citation statements)

References 39 publications

(44 reference statements)

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“…25 Another explanation could be that in this malignant disease the immune system of the patients might be more deteriorated. 26 Nevertheless, in contrast from reports of the use of other antiidiotype MAb in a different ganglioside model in SCLC patients (7 and 8), evident antibody responses against both, the murine immunoglobulin and NeuGc-GM3 ganglioside, were reached in most of our patients due to the immunization protocol with 1E10 MAb vaccine. Although the patients were repeatedly injected with 1E10 MAb vaccine and that this vaccination regimen generated strong antibody responses to the murine immunoglobulin, only a low rate of side effects was observed, confirming previous reports about the safety of the treatment with this anti-idiotype vaccine.…”

Section: Discussioncontrasting

confidence: 50%

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Neninger¹,

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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ABSTRACT1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

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Section: Discussioncontrasting

confidence: 50%

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Neninger¹,

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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“…The degree of macrophage infiltration into human non-small cell lung cancers is correlated with the microvessel counts and inversely correlated with survival (21). In addition, alveolar-derived macrophages isolated by bronchoalveolar lavage (BAL) from lung cancer patients have altered in vitro characteristics (26). In transgenic mouse models, elevating the number of pulmonary macrophages overexpressing FGF10 in type 2 and Clara cells induced spontaneous development of lung tumors in the absence of exogenous carcinogens (27).…”

Section: Introductionmentioning

confidence: 99%

A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment

et al. 2008

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One area of intensive investigation is to understand complex cellular and signaling interactions in the tumor microenvironment. Using a novel, although straightforward, microarray approach, we defined a gene expression signature from the lung tumor microenvironment in the murine A/J-urethane model of human lung adenocarcinoma. The tumor microenvironment is reflected by the composition of the cell types present and alterations in mRNA levels, resulting in a ''Field Effect'' around the tumor. The genes composing the Field Effect expression signature include proteases and their inhibitors, inflammation markers, and immune signaling molecules. By several criteria, the Field Effect expression signature can be attributed to the macrophage lineage, suggesting a qualitative change in the expression pattern of tumor-associated macrophages (TAM) observed in lung tumors. The protein expression levels for a number of Field Effect genes were verified by Western blot analysis of lung homogenates, and for their expression in macrophages and parenchymal cells outside of the tumors by immunohistochemistry. In addition, the Field Effect expression signature was used to classify bronchoalveolar lavage (BAL) cells from tumor-bearing or age-matched control mice. Using a variety of statistical measures, the Field Effect expression signature correctly classified the BAL cells >94% of the time. Finally, the protein levels for several Field Effect genes were higher in cellfree BAL fluid, indicating they may be secreted by the TAMs. This work suggests that TAMs generate a unique gene expression signature within the tumor microenvironment, and this signature could potentially be used for identifying lung cancer from BAL cells and/or fluid. [Cancer Res 2008;68(1):34-43]

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“…42 Poor antigen-presenting capacity is a common characteristic of TAMs, and abundant evidence indicates that T cells undergo inhibitory regulation and become anergic in tumor-bearing hosts. 13,43,44 Several mechanisms, including induction of structural abnormalities of T-cell receptor complex, 45,46 production of immunosuppressive cytokines, 8 or reduced expression of MHC-II molecules, 14,47,48 have been proposed to account for T-cell unresponsiveness. However, the molecular mechanism leading to MHC-II down-regulation on TAMs has never been reported before.…”

mentioning

confidence: 99%

Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3

Chang

Chen

Lee

et al. 2008

Blood

110

104

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Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors originating from a diversity of lineages. DcR3 is capable of promoting angiogenesis, inducing dendritic cell apoptosis, and modulating macrophage differentiation. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most malignant tumors, we used microarray technology to investigate whether DcR3 contributes to the development of TAMs. Among the DcR3-modulated genes expressed by TAMs, those that encode proteins involved in MHC class II (MHC-II)-dependent antigen presentation were down-regulated substantially, together with the master regulator of MHC-II expression (the class II transactivator, CIITA). The ERK- and JNK-induced deacetylation of histones associated with the CIITA promoters was responsible for DcR3-mediated down-regulation of MHC-II expression. Furthermore, the expression level of DcR3 in cancer cells correlated inversely with HLA-DR levels on TAMs and with the overall survival time of pancreatic cancer patients. The role of DcR3 in the development of TAMs was further confirmed using transgenic mice overexpressing DcR3. This elucidates the molecular mechanism of impaired MHC-II-mediated antigen presentation by TAMs, and raises the possibility that subversion of TAM-induced immunosuppression via inhibition of DcR3 expression might represent a target for the design of new therapeutics.

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Alveolar macrophage function is altered in patients with lung cancer

Cited by 38 publications

References 39 publications

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment

Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3

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