Prognostic impact of CD57, CD68, M-CSF, CSF-1R, Ki67 and TGF-beta in soft tissue sarcomas

Sørbye, Sveinung Wergeland; Kilvaer, Thomas K.; Valkov, Andrey Yurjevich; Dønnem, Tom; Smeland, Eivind; Al-Shibli, Khalid; Bremnes, Roy M.; Busund, Lill-Tove

doi:10.1186/1472-6890-12-7

Cited by 24 publications

(27 citation statements)

References 40 publications

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“… 42 Overexpression of TGFβ(s) correlates with tumor progression and poor prognosis 40 , 43 in many types of cancer, including soft tissue sarcomas in which one analysis of 249 patients showed that elevated tumor expression of TGFβ significantly correlated with poor disease-specific survival. 44 Thus, control of TGFβ(s) expression could potentially be used as a justification for anticancer immune induction.…”

Section: Discussionmentioning

confidence: 99%

Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma

et al. 2015

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We report on 12 consecutive patients with advanced/metastatic Ewing's sarcoma who were treated as a separate cohort of a phase 1 trial of FANG autologous immunotherapy (1 × 106–2.5 × 107 cells/intradermal injection each month for minimum 4 months). Safety and clinical response were monitored. Patient immune response to unmodified autologous tumor cells was assessed by gamma interferon-enzyme-linked immunospot (γIFN-ELISPOT) assay using peripheral blood mononuclear cells from baseline (pretreatment) and multiple postvaccination time points. None of the 12 patients (47 vaccinations) developed grade 2/3/4 drug-related toxicity. Median product release granulocyte-macrophage colony-stimulating factor expression was 1,941 pg/106 cells, and TGFβ1and TGFβ2 knockdown were 99 and 100%, respectively. Eight patients were assessed for ELISPOT response to autologous tumor cells at baseline and all (100%) were negative. In contrast, follow-up ELISPOT response at month 1 or month 4 (one patient) after FANG was positive in all eight patients. One patient achieved a partial tumor response (38% tumor reduction, RECIST 1.1). The Kaplan–Meier estimated survival of these 12 patients at 1 year was 75%. In this phase 1 study in patients with Ewing's sarcoma, FANG immunotherapy was well tolerated, elicited a tumor-specific systemic immune response in all patients, and was associated with favorable 1-year survival. Further clinical testing is indicated.

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Section: Discussionmentioning

confidence: 99%

Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma

et al. 2015

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“…Confirming the importance of a spatial distribution of NK cells in tumor tissue, Al-Shibli et al [8] showed that high density of stromal NK cells was an independent positive prognostic factor for disease-specific survival in pulmonary carcinoma, whereas high density of NK cells within tumor islets was not. On the other hand, in soft tissue sarcomas, there was no correlation between NK cell density in tumors or peritumoral tissues and the patients’ prognosis [9]. …”

Section: Immune Cells With the Anti-tumor Functionsmentioning

confidence: 99%

Clinical evaluation of systemic and local immune responses in cancer: time for integration

Gutkin

Shurin

2013

Cancer Immunol Immunother

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The immune system has a dual role in cancer development and progression. On the one hand, it can eradicate emerging malignant cells, but on the other hand, it can actively promote growth of malignant cells, their invasive capacities and their ability to metastasize. Immune cells with predominantly anti-tumor functionality include cells of the innate immune system, such as natural killer cells, and cells of adaptive immunity, such as conventional dendritic cells and cytotoxic T lymphocytes. Immune cells with predominantly pro-tumor functionality include a broad spectrum of cells of the innate and adaptive immune system, such as type 2 neutrophils and macrophages, plasmacytoid DC, myeloid-derived suppressor cells and regulatory T lymphocytes. The presence of immune cells with tumor-suppressive and tumor-promoting activity in the cancer microenvironment and in peripheral blood is usually associated with good clinical outcomes and poor clinical outcomes, respectively. Significant advances in experimental and clinical oncoimmunology achieved in the last decade open an opportunity for the use of modern morphologic, flow cytometric and functional tests in clinical practice. In this review, we describe an integrated approach to clinical evaluation of the immune status of cancer patients for diagnostic purposes, prognostic/predictive purposes (evaluation of patient prognosis and response to treatment) and for therapeutic purposes.

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“…Expression of the Ki67 protein (pKi67) is associated with the proliferative activity of intrinsic cell populations in malignant tumors, allowing it to be used as a marker of tumor aggressiveness (5,6). The prognostic value of pKi67 has been investigated in a number of studies with its potential as a reliable marker having been shown in cancers of the breast, soft tissue, lung, prostate, cervix and central nervous system (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Ki67 is a promising molecular target in the diagnosis of cancer (Review)

Jiang

Chen

et al. 2014

Molecular Medicine Reports

632

445

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The expression of Ki67 is strongly associated with tumor cell proliferation and growth, and is widely used in routine pathological investigation as a proliferation marker. The nuclear protein Ki67 (pKi67) is an established prognostic and predictive indicator for the assessment of biopsies from patients with cancer. Clinically, pKi67 has been shown to correlate with metastasis and the clinical stage of tumors. In addition, it has been shown that Ki67 expression is significantly higher malignant tissues with poorly differentiated tumor cells, as compared with normal tissue. According to its predictive role, pKi67 expression identifies subpopulations of patients who are more likely to respond to a given therapy. The Ki67 labeling index is an independent prognostic factor for survival rate, which includes all stages and grade categories. There is a correlation between the ratio of Ki67‑positive malignant cells and patient survival. It has been shown that blocking of Ki67 either by microinjection of antibodies or through the use of antisense oligonucleotides leads to the arrest of cell proliferation. Specifically, antisense oligonucleotides and antibodies against pKi67 have been shown to inhibit the progression of the cell cycle. The Ki67 protein is well characterized at the molecular level and is extensively used as a prognostic and predictive marker for cancer diagnosis and treatment. Increasing evidence indicates that Ki67 may be an effective target in cancer therapy. It therefore merits further development, including testing in more sophisticated in vitro and appropriate in vivo models. This review provides an overview of recent advances in this field.

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Prognostic impact of CD57, CD68, M-CSF, CSF-1R, Ki67 and TGF-beta in soft tissue sarcomas

Cited by 24 publications

References 40 publications

Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma

Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma

Clinical evaluation of systemic and local immune responses in cancer: time for integration

Ki67 is a promising molecular target in the diagnosis of cancer (Review)

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