Immune infiltrate in sarcomas

Abstract

Sarcomas are malignant tumors emerging from mesenchymal tissues including bone, cartilage, adipose tissue and muscle. Sarcomas are rare, accounting for only 2 to 3 percent of all adult cancers. Underlying pathogenic mechanisms are slowly beginning to be understood and in about a third of sarcomas include unique chromosomal translocations that generate fusion genes, which encode fusion proteins most of which function as aberrant transcription factors. However, two thirds of sarcoma harbor complex genetic alterations that preclude clear assessment of their pathogenesis. Numerous studies suggest that the immune system has an important role in the control of tumor progression. It is documented that patients with tumors having a strong cytotoxic T cell infiltrate have a better overall survival rate than those with tumors that do not. It is also well known that cancer can evade the host immune defenses. Thus it seems important to characterize tumor immune infiltrates and determine their precise role with regard to tumor growth. Unlike other types of cancer, immune infiltrates in sarcomas have been little studied. The aim of this study is to characterize the phenotype of immune cell populations infiltrating different types of sarcomas. Samples of seven types of sarcomas have been analyzed. Following tumor dissociation, immune infiltrates were analyzed by flow cytometry. Our preliminary results show myeloid cells to be the dominant population, followed by small amounts of T cells. The myeloid population is heterogeneous and is composed of different cell subsets, including macrophages (HLADR+CD11b+) and cells displaying HLADR- plus a combination of CD11b+ CD15+ and CD33+ phenotypes. These cells could correspond to myeloid-derived suppressor cells (MDSCs), which are strongly immunosuppressive and promote tumor growth and metastasis. Different T cell subpopulations have also been found. The dominant subset consists of CD4+ T cells, typically associated with helper functions. Samples with high levels of CD4+ T cells and CD25+Foxp3+ T cell (that correspond to regulatory cells) had low counts of CD4-/CD8+ T cells that are associated with cytotoxic functions. Immune cell infiltrates in sarcomas are poorly described in the literature. A better phenotypic and functional characterization of these cells could probably help in the development of new therapeutic strategies