Structured myeloid cells and anti-angiogenic therapy in alveolar soft part sarcoma
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COMMENTARY
Open Access
Structured myeloid cells and anti-angiogenic therapy in alveolar soft part sarcoma Chiara Castelli1, Marcella Tazzari1, Tiziana Negri2, Barbara Vergani3, Licia Rivoltini1*, Silvia Stacchiotti4 and Silvana Pilotti2 Abstract Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma and the clinical management of patients with unresectable, metastatic disease is still challenging. ASPS expresses an array of potentially therapeutically targetable, angiogenesis-related molecules and, importantly, it has a distinctive angiogenic phenotype marked by a peculiar tumor-associated vasculature. Several studies, conducted in transgenic mouse models and in a large variety of human tumors of different histotype, clearly proved the substantial contribution of tumor-infiltrating myeloid cells, such as myeloid derived suppressor cells, monocytes and macrophages, in the formation and maintenance of abnormal blood vessels in tumors. By immunohistochemistry we thus explored the presence and the distribution of cells expressing myeloid markers in the inflammatory infiltrate of surgical treated metastatic ASPS. Indeed, we found that myeloid cells expressing CD14 and CD163 markers constitute the prominent cells in the inflammatory infiltrate of ASPS. These macrophage-like cells form a network surrounding the endothelial cells, or, interspersed in the tumor nest, they keep deep contact with tumor cells. In this commentary, we discussed our findings in relation to the recently published paper by Kummar and colleagues reporting the clinical and molecular results of a phase II clinical trial in patients with unresectable, metastatic ASPS treated with the anti-angiogenic drug cediranib, targeting the VEGFR-1,-2,-3 tyrosine kinases. Keywords: Immune infiltrating cells, Inflammation, Myeloid cells, Soft tissue sarcoma, Anti-angiogenic therapy
Commentary We read with great interest the paper by Kummar et al. on cediranib in metastatic alveolar soft part sarcoma (ASPS) [1]. The study evaluated the antitumor activity of cediranib in 43 patients. The disease control rate (partial response plus stable disease) of patients who completed the therapy course was 84%. Tumor biopsies prior and after one week of cediranib were obtained from a subset of patients. Thus, the authors investigated for the first time the gene expression changes in ASPS after anti-angiogenic treatment, giving a comprehensive overview of the microarray/qRT-PCR profiles of significantly modulated genes in 7 validated cases. Included in this list are genes playing a direct role in the cancer driven neo-angiogenesis. Tumor lesions from patients treated with cediranib displayed a selective down-regulation of angiopoietin 2 (ANGPT2) and * Correspondence: [email protected] 1 Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan 20133, Italy Full list of author information is available at the end of the article
the up-regulation of its receptor TIE2. This opposite gene modulation
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