Structured myeloid cells and anti-angiogenic therapy in alveolar soft part sarcoma.
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.
Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G, Venezian 1, Milan 20133, Italy. Licia.Rivoltini@istitutotumori.mi.it.
Chiara
C
Castelli
Marcella
M
Tazzari
Tiziana
T
Negri
Barbara
B
Vergani
Licia
L
Rivoltini
Silvia
S
Stacchiotti
Silvana
S
Pilotti
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects / Q000473:pathology*; D009362:Neoplasm Metastasis; D018234:Sarcoma, Alveolar Soft Part / Q000188:drug therapy* / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects
D020533:Angiogenesis Inhibitors