Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

Chimal-Ramírez, Gloria Karina; Espinoza-Sánchez, Nancy Adriana; Fuentes‐Pananá, Ezequiel M.

doi:10.1155/2013/835956

Cited by 56 publications

(62 citation statements)

References 164 publications

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“…Depending on the dominant cellular subtypes, protumor or antitumor effects are expected . M2 macrophages, regulatory T cells, and N2 neutrophils have been considered to have protumor activity . Both granulocytic lineage MDSCs and TANs have gained much more relevance recently and, because of the similarities of their protumoral and phenotypic characteristics, their distinction has not been simple .…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3‐dioxygenase and tryptophan 2,3‐dioxygenase expression in HPV infection, SILs, and cervical cancer

Venancio

Consolaro

Derchain

et al. 2019

Cancer Cytopathology

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BACKGROUND: Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer. METHODS: IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n = 6), high-grade SIL (n = 30), or squamous cell carcinoma (SCC) (n = 6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis. RESULTS: Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins. CONCLUSIONS: The upregulation of IDO expression in leukocytes and squamous cells in HPVassociated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source.We gratefully acknowledge the collaboration of Luiz Carlos Zeferino, Júlio Cesar Teixeira, and Luiz Bahamondes for their assistance to the women included in this study and Maria Cecília Costa and Fabrícia Gimenez for their assistance with polymerase chain reaction analyses.Additional supporting information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3‐dioxygenase and tryptophan 2,3‐dioxygenase expression in HPV infection, SILs, and cervical cancer

Venancio

Consolaro

Derchain

et al. 2019

Cancer Cytopathology

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“…Both experimental and clinical studies have shown that the tumor microenvironment shifts Ma and other immune cells to perform functions related to the tumor’s needs (oncotraining). These functions are related to chronic inflammation and tissue remodeling and include increased proliferation and survival, increased angiogenesis and vessel permeability, and self-renewal properties that together promote tumor growth and metastasis [19, 20]. …”

Section: Discussionmentioning

confidence: 99%

Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment

et al. 2015

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Gold-based nanoparticles have been used in a number of therapeutic and diagnostic applications. The purpose of this study was to investigate the efficacy of gold–silica nanoshells (AuNS) in photothermal therapy (PTT) of rat gliomas. Rat alveolar macrophages (Ma) were used as nanoparticle delivery vectors. Uptake of AuNS (bare and PEGylated) was investigated in Ma. AuNS were incubated with Ma for 24 h. Phase contrast microscopy was used to visualize the distribution of loaded Ma in three-dimensional glioma spheroids. PTT efficacy was evaluated for both empty (Ma) and AuNS-loaded Ma (MaNS) in both monolayers and spheroids consisting of C6 rat glioma cells and Ma. Monolayers/spheroids were irradiated for 5 min with light from an 810-nm diode laser at irradiances ranging from 7 to 28 W cm−2. Monolayer survival was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay while PTT efficacy in spheroids was determined from growth kinetics and live/dead fluorescence microscopy. PTT efficacy was investigated in vivo using a Sprague–Dawley rat glioma model. Five rats received direct intracranial injection of a mixture of 104 C6 glioma cells and, 2 days later, an equal number of MaNS. Three rats received laser treatment (810 nm; 10 min; 1 W) while the remaining two served as controls (no laser treatment). The uptake ratio of bare to PEGylated AuNS by Ma was 4:1. A significant photothermal effect was observed in vitro, albeit at relatively high radiant exposures (2.1–4.2 kJ cm−2). PTT proved effective in vivo in preventing or delaying tumor development in the PTT-treated animals.

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“…All stromal cells participate in the progression of the tumor, probably providing direct cell to cell and cell to ECM interactions, and from the soluble factors they secrete. Tumors are actively recruiting immune cells; however, tumor-associated immune cells often lack immunosurveillance activities, and instead they fulfill protumoral functions (for a comprehensive review see [43]). How tumors favor this immunological switch is not completely understood.…”

Section: Discussionmentioning

confidence: 99%

MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

Chimal-Ramírez

Espinoza-Sánchez

Utrera-Barillas

et al. 2013

BioMed Research International

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Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

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Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

Cited by 56 publications

References 164 publications

Indoleamine 2,3‐dioxygenase and tryptophan 2,3‐dioxygenase expression in HPV infection, SILs, and cervical cancer

Indoleamine 2,3‐dioxygenase and tryptophan 2,3‐dioxygenase expression in HPV infection, SILs, and cervical cancer

Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment

MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

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