The Suppressive Tumor Microenvironment: A Challenge in Cancer Immunotherapy

Vasievich, Elizabeth A.; Huang, Leaf

doi:10.1021/mp1004228

Cited by 170 publications

(113 citation statements)

References 71 publications

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“…Thus, while M-chlorin may accumulate on the systemic populations of M2 macrophages, the cytotoxic effects of M-chlorin PDT might only affect the tumor microenvironment under irradiation. Peptide therapy or DNA vaccine therapy against M2 macrophages expressing high levels of mannose receptors were reported to be beneficial against cancer (16,20,22), but these therapies attack not only TAMs in cancer stroma, but also M2 macrophages throughout the body, risking the induction of immunosuppression. Such a risk would not be an issue with our M-chlorin PDT therapy, which targets only TAMs in tumor stroma and thus should not affect immune responses elsewhere.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

Hayashi,

Kataoka,

Yano

et al. 2015

Molecular Cancer Therapeutics

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Tumor-associated macrophages (TAM) in cancer stroma play important roles for cancer cell growth, invasion, angiogenesis, and metastases. We synthesized a novel photosensitizer, mannose-conjugated chlorin (M-chlorin), designed to bind mannose receptors highly expressed on TAMs. We evaluated the newly available photodynamic therapy (PDT) with M-chlorin against gastric and colon cancer. We evaluated PDT with Mchlorin for in vitro cytotoxicity and apoptosis induction in cancer cells compared with chlorin alone and glucose-conjugated chlorin (G-chlorin). The subcellular localization of Mchlorin was observed by confocal microscopy, and the Mchlorin PDT effects against TAMs including THP-1-induced M2-polarized macrophages were evaluated. Anticancer effects were also investigated in an allograft model where cytotoxic effects against TAMs in the cancer cell stroma were analyzed by immunohistochemistry. M-chlorin PDT strongly induced cell death in cancer cells to almost the same extent as G-chlorin PDT by inducing apoptosis. M-chlorin was incorporated into cancer cells where it localized mainly in lysosomes and endoplasmic reticula. M-chlorin PDT revealed strong cytotoxicity for M2 macrophages induced from THP-1 cell lines, and it induced stronger cytotoxicity than G-chlorin PDT in the allograft model through killing both cancer cells and TAMs in the cancer stroma. The M-chlorin PDT produced strong cytotoxicity against cancer tissue by inducing apoptosis of both cancer cells and TAMs in the cancer stroma. This novel PDT thus stands as a new candidate for very effective, next-generation PDT. Mol Cancer Ther; 14(2); 452-60. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

“…TAMs are known to specifically express abundant levels of CD206, a mannose receptor (15)(16)(17), which is also called the "pattern-recognition receptor." These receptors are crucial for the macrophage's role in engulfing invading organisms and degrading them through endocytosis and phagocytosis (18,19).…”

Section: Introductionmentioning

confidence: 99%

A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

Hayashi,

Kataoka,

Yano

et al. 2015

Molecular Cancer Therapeutics

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“…þ Tregs increase in patients with cancer, 1,[6][7][8][9][10] and their presence correlates with unfavourable prognosis. CD8 þ…”

Section: Cd25mentioning

confidence: 99%

Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer

Chen

et al. 2015

J Int Med Res

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“…Antibodies possess several clinically relevant mechanisms of action. They can manipulate tumor-related signaling and various antibodies show immunomodulatory properties and, by activation or inhibition of the immune system, they can induce antitumor immune responses [394,395]. Specifically, Fc-receptor expressing immune cells mediate the killing of tumor cells by mAbs.…”

Section: Antibodiesmentioning

confidence: 99%

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

Schwendener¹,

Mete²

2013

Frontiers in Clinical Drug Research - Anti-Cancer Agents

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Solid tumors grow within a complex microenvironment composed of diverse cell types such as fibroblasts, endothelial cells, mast cells, macrophages and 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 tumor microenvironment (TME) is increasingly being explored as a potential therapeutic target for which novel strategies are developed. lt;/pgt;lt;pgt; This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed. This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed.

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The Suppressive Tumor Microenvironment: A Challenge in Cancer Immunotherapy

Cited by 170 publications

References 71 publications

A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

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