Tumor and Microenvironment Modification during Progression of Murine Orthotopic Bladder Cancer

Tham, Sin Mun; Ng, Kee H; Pook, Sim Hwee; Esuvaranathan, Kesavan; Mahendran, Ratha

doi:10.1155/2011/865684

Cited by 24 publications

(19 citation statements)

References 42 publications

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“…Indeed, reports from our and other laboratories have indicated that decline of tumor load causes a shift of cytokine balance in tumor microenvironment. 14,16,17,19,20,24,30 The possibility of Listeria exposure directly inducing tumor cells death is, however, ruled out as exposure of tumor cells to Listeria in vitro did not alter their survival (data not shown). Thus, next we explored other possible causes of tumor cell death after Listeria administration.…”

Section: Discussionmentioning

confidence: 99%

Augmented Macrophage Differentiation and Polarization of Tumor-associated Macrophages Towards M1 Subtype in Listeria-administered Tumor-bearing Host

Rakesh

Vishvakarma

Mohapatra

et al. 2012

Journal of Immunotherapy

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This study investigates the effect of Listeria administration on differentiation of macrophages from precursor bone marrow cells and functional status of tumor-associated macrophages (TAM). Listeria administration not only resulted in an augmented infiltration of tumor by F4/80 macrophages but also repolarized the functional status of TAM displaying features of some M1 macrophage subtype with upregulated phagocytosis and tumoricidal activity accompanied by altered expression of monocarboxylate transporter-1, toll-like receptor-2, surface markers: CD11c, interleukin-2 receptor, CD62L, and secreted molecules: nitric oxide, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor. Declined tumor cell survival and modulated repertoire of cytokines: interferon-γ, IL-6, IL-10, and transforming growth factor-β in tumor microenvironment indicated their role in polarization of TAM towards proinflammatory state. Bone marrow cell of Listeria-administered tumor-bearing mice showed augmented survival, declined expression of p53 upregulated modulator of apoptosis with an upregulated differentiation into activation responsive bone marrow-derived macrophages along with altered expression of macrophage-colony stimulating factor, macrophage-colony stimulating factor receptor, and granulocyte macrophage-colony stimulating factor receptor. These findings indicate that Listeria infection is associated with an augmented differentiation of macrophages accompanied by tumoricidal activation of TAM.

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Section: Discussionmentioning

confidence: 99%

Augmented Macrophage Differentiation and Polarization of Tumor-associated Macrophages Towards M1 Subtype in Listeria-administered Tumor-bearing Host

Rakesh

Vishvakarma

Mohapatra

et al. 2012

Journal of Immunotherapy

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“…However, the Th1/Th2 balance changed depending on the time after bladder cancerogenesis; while GATA3 decreased at day 7, T effector cells significantly increased at day 28 [32]. Therapeutic strategies with a bimodal function inducing a Th1 response and blocking a pre-therapeutic Th2 milieu in Th2-dominated tumors have shown to improve responses to immunotherapy [32–33]. Also BCG is thought to be a Th1-polarized immunomodulator [34].…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer

et al. 2016

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Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-muscle-invasive bladder cancer, approximately 30% of patients are unresponsive to treatment. New biomarkers are important to identify patients who will benefit most from BCG during a worldwide BCG shortage. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded tissue sections of bladder cancer by immunohistochemistry, using monoclonal antibodies to tumor-associated macrophages (TAMs; CD68, CD163), B-lymphocytes (CD20) and T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3 and CD25). Cell densities in the lamina propria without invasion, at the invasive front if present, in the papillary tumor stroma, and in the neoplastic urothelium were calculated. Twenty-nine (72.5%) of 40 patients were classified as BCG responders after a mean follow-up of 35.3 months. A statistically significant association was observed for BCG failure with low density of CD4+ and GATA3+ T-cells, and increased expression of FOXP3+ and CD25+ regulatory T-cells (Tregs) as well as CD68+ and CD163+ TAMs. Survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with an increased count of CD4+ and GATA3+ T-cells. TAMs, Tregs and T-bet+ T-cells were inversely correlated with RFS. Thus, the tumor microenvironment seems to influence the therapeutic response to BCG, permitting an individualized treatment.

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“…With the recent discovery of all of the fifteen members of the KLK family, increasing evidence has indicated that KLKs may play pivotal roles in breast cancer progression and metastasis (Table 4, Figure 1,2). 6,63–65 In normal breast tissue, all fifteen KLKs have been identified, either at the mRNA and/or the protein level 23,66. KLK15 mRNA is not expressed by normal breast tissue, low to moderate mRNA levels are detected for KLK2–5, 9, 12 and 13 , high ones for KLK1, 6–8, 10, 11 and 14.…”

Section: Klk Expression In Breast Cancermentioning

confidence: 99%

Emerging clinical importance of the cancer biomarkers kallikrein-related peptidases (KLK) in female and male reproductive organ malignancies

Schmitt¹,

Magdolen²,

Yang³

et al. 2013

Radiology and Oncology

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BackgroundTumor tissue-associated KLKs (kallikrein-related peptidases) are clinically important biomarkers that may allow prognosis of the cancer disease and/or prediction of response/failure of cancer patients to cancer-directed drugs. Regarding the female/male reproductive tract, remarkably, all of the fifteen KLKs are expressed in the normal prostate, breast, cervix uteri, and the testis, whereas the uterus/endometrium and the ovary are expressing a limited number of KLKs only.ConclusionsMost of the information regarding elevated expression of KLKs in tumor-affected organs is available for ovarian cancer; depicting them as valuable biomarkers in the cancerous phenotype. In contrast, for breast cancer, a series of KLKs was found to be downregulated. However, in breast cancer, KLK4 is elevated which is also true for ovarian and prostate cancer. In such cases, selective synthetic KLK inhibitors that aim at blocking the proteolytic activities of certain KLKs may serve as future candidate therapeutic drugs to interfere with tumor progression and metastasis.

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Tumor and Microenvironment Modification during Progression of Murine Orthotopic Bladder Cancer

Cited by 24 publications

References 42 publications

Augmented Macrophage Differentiation and Polarization of Tumor-associated Macrophages Towards M1 Subtype in Listeria-administered Tumor-bearing Host

Augmented Macrophage Differentiation and Polarization of Tumor-associated Macrophages Towards M1 Subtype in Listeria-administered Tumor-bearing Host

Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer

Emerging clinical importance of the cancer biomarkers kallikrein-related peptidases (KLK) in female and male reproductive organ malignancies

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