Special Issue "Tumor Associated Macrophages"

Quicklinks

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 September 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Reto Schwendener (Website)

Institute of Molecular Cancer Research, Laboratory of Liposome Research, University of Zurich, CH-8057 Zurich, Switzerland
Phone: +41-44-635-3483
Interests: tumor microenvironment; stromal cells; macrophages; tumor associated macrophages; neutrophils; tumor associated neutrophils; myeloid derived suppressor cells; immune cells; fibroblasts; stromal interactions; bisphosphonates; clodronate; macrophage depletion; liposomes; nanocarriers; nanomedicine; therapeutic targets; repolarization; reprogramming; immunotherapy; adjuvant cancer therapy; therapies aiming at the tumor microenvironment

Special Issue Information

Dear Colleagues,

This issue invites experts to contribute original research reports as well as review articles that describe studies on tumor associated macrophages (TAM) and other immune cells that infiltrate the tumor microenvironment (TME) and that either promote or inhibit growth, invasion and spread of tumors. Solid tumors grow within a complex microenvironment composed of diverse cell types such as fibroblasts, endothelial cells, mast cells, macrophages and other immune cells that are attracted by tumor cell derived factors and embedded in an extracellular matrix. Molecular and cellular interactions between epithelial cells and cells surrounding the tumor stroma promote growth, invasion and spread of tumors. To delay or impede tumor growth, the TME is increasingly being explored as a potential therapeutic target for which novel strategies are developed.

Contributions describing biological function and properties of the TME and drugs or treatments that aim at the repolarization of a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment are welcome.
Potential topics include, but are not limited to:
• Biology of the TME with emphasis on TAM or other immune cells that infiltrate the TME
• Description of new findings related to interactions of tumor cells with the TME
• Therapy concepts aiming at the TME to inhibit tumor growth
• Development of novel drug carrier systems for TME targeting

Prof. Dr. Reto Schwendener
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).

Keywords

  • tumor microenvironment
  • macrophages
  • tumor associated macrophages
  • immune cells
  • stromal interactions
  • repolarization, reprogramming
  • immunotherapy, adjuvant cancer therapy
  • macrophage depletion
  • drug targeting

Published Papers (5 papers)

View options order results:
result details:
Displaying articles 1-5
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue
Cancers 2015, 7(1), 143-178; doi:10.3390/cancers7010143
Received: 8 October 2014 / Accepted: 5 January 2015 / Published: 15 January 2015
Cited by 7 | PDF Full-text (947 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT [...] Read more.
The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity. Full article
(This article belongs to the Special Issue Tumor Associated Macrophages)
Open AccessArticle Specific Inhibition of the VEGFR-3 Tyrosine Kinase by SAR131675 Reduces Peripheral and Tumor Associated Immunosuppressive Myeloid Cells
Cancers 2014, 6(1), 472-490; doi:10.3390/cancers6010472
Received: 18 November 2013 / Revised: 6 February 2014 / Accepted: 17 February 2014 / Published: 28 February 2014
Cited by 3 | PDF Full-text (1174 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) represent prominent components in cancer progression. We previously showed that inhibition of the VEGFR-3 pathway by SAR131675 leads to reduction of TAM infiltration and tumor growth. Here, we found that treatment with SAR131675 [...] Read more.
Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) represent prominent components in cancer progression. We previously showed that inhibition of the VEGFR-3 pathway by SAR131675 leads to reduction of TAM infiltration and tumor growth. Here, we found that treatment with SAR131675 prevents the accumulation of immunosuppressive blood and splenic MDSCs which express VEGFR-3, in 4T1 tumor bearing mice. Moreover we showed that soluble factors secreted by tumor cells promote MDSCs proliferation and differentiation into M2 polarized F4/80+ macrophages. In addition, cell sorting and transcriptomic analysis of tumor infiltrating myeloid cells revealed the presence of a heterogeneous population that could be divided into 3 subpopulations: (i) immature cells with a MDSC phenotype (GR1+/CD11b+/F4/80); (ii) “immuno-incompetent” macrophages (F4/80high/CD86neg/MHCIILow) strongly expressing M2 markers such as Legumain, CD206 and Mgl1/2 and (iii) “immuno-competent”-M1 like macrophages (F4/80Low/CD86+/MHCIIHigh). SAR131675 treatment reduced MDSCs in lymphoid organs as well as F4/80High populations in tumors. Interestingly, in the tumor SAR131675 was able to increase the immunocompetent M1 like population (F4/80low). Altogether these results demonstrate that the specific VEGFR-3 inhibitor SAR131675 exerts its anti tumoral activity by acting on different players that orchestrate immunosuppression and cancer progression in a tumoral context: MDSCs in peripheral lymphoid organs and TAMs infiltrating the tumor. Full article
(This article belongs to the Special Issue Tumor Associated Macrophages)
Open AccessArticle Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis
Cancers 2013, 5(4), 1643-1654; doi:10.3390/cancers5041643
Received: 1 October 2013 / Revised: 16 November 2013 / Accepted: 25 November 2013 / Published: 4 December 2013
PDF Full-text (1216 KB) | HTML Full-text | XML Full-text
Abstract
Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before [...] Read more.
Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer. Full article
(This article belongs to the Special Issue Tumor Associated Macrophages)

Review

Jump to: Research

Open AccessReview Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment
Cancers 2014, 6(3), 1670-1690; doi:10.3390/cancers6031670
Received: 26 May 2014 / Revised: 27 July 2014 / Accepted: 5 August 2014 / Published: 13 August 2014
Cited by 68 | PDF Full-text (2746 KB) | HTML Full-text | XML Full-text
Abstract
During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their [...] Read more.
During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy. Full article
(This article belongs to the Special Issue Tumor Associated Macrophages)
Open AccessReview Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!
Cancers 2014, 6(1), 297-322; doi:10.3390/cancers6010297
Received: 12 November 2013 / Revised: 8 January 2014 / Accepted: 14 January 2014 / Published: 27 January 2014
Cited by 7 | PDF Full-text (1209 KB) | HTML Full-text | XML Full-text
Abstract
Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous [...] Read more.
Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mfs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-b, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health. Full article
(This article belongs to the Special Issue Tumor Associated Macrophages)

Journal Contact

MDPI AG
Cancers Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
cancers@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Cancers
Back to Top