Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

Abstract

BackgroundTumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.MethodsIn order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.ResultsWhile TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.ConclusionsOur data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.

Effect of mesenchymal stem cells on hypoxia-induced desensitization of β2-adrenergic receptors in rat osteosarcoma cells

“…Conversely, several groups have emphasized a supportive role of MSCs, a heterogeneous stromal cellular population, as a member of the tumor microenvironment. Johann et al (25) reported that tumor stromal cells derived from 11 cases of pediatric malignancies, including two cases of OS, exhibited MSC-like properties and impaired NK cell cytotoxicity. Brune et al (26) examined six cases of OS and reported that non-malignant MSCs were isolated from human primary OS samples, stressing the hypothesis that bone-marrow MSCs may be related to tumor stromal MSCs.…”

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

“…37 Accurate characterization of EWS including HLA I, GD2 and CD58 surface Ag expression may help to elucidate candidates suitable and those unsuitable for NK cell-based immunotherapy. [38][39][40] Transfer of expanded or activated haploidentical NK cells could be used to enhance antitumor activity and has been shown to be feasible and safe in numerous pilot studies. 41,42 In conclusion, multimodal treatment of primary metastatic and relapsed metastatic stage IV EWS including haploidentical stem cell transplantation can facilitate long-term remission and survival.…”

In Vitro Evidence of the Presence of Mesenchymal Stromal Cells in Cervical Cancer and Their Role in Protecting Cancer Cells from Cytotoxic T Cell Activity

“…Such processes have been implicated in several aspects of epithelial tumor biology, such as tumor growth, neoplastic progression, angiogenesis, and metastasis [6,7]. MSCs have been isolated from different tumor types such as ovarian carcinomas [8], giant cell tumors of bone [9], neuroblastomas [10], osteosarcomas [11], lipomas [12], and gastric cancer [13]; however, the presence of MSCs in cervical cancer (CeCa) and their possible role in such tumor growth have not been documented.…”

“…the isolation of MSCs from several tumors [8][9][10][11][12][13]; however, the presence of MSCs has not been demonstrated in NCx or in CeCa tissue. Following this, and taking into consideration the immunossupressive properties of MSCs [35], we reasoned that the presence of these cells in cervical tumors may represent an important immunoselective advantage for tumor cells to evade the immune recognition.…”