Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma

Lezot

2019

Cellular Immunology

164

176

Section: Lymphocytes Subpopulations In Osteosarcoma and Therapeutic Imentioning

confidence: 99%

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

Lezot

2019

Cellular Immunology

164

176

“…Preclinical data suggest a role for tumor-infiltrating lymphocytes in osteosarcoma (25,26), while several cytokines, including IL-12, IL-2, and type I interferons, have shown preclinical activity (27)(28)(29). Adjuvant use of muramyl tripeptide phosphatidylethanolamine (mifamurtide), a synthetic lipophilic analog of a mycobacterial cell wall protein, was recently shown to improve survival of patients with osteosarcoma (30) and has been approved for clinical use.…”

Section: Introductionmentioning

confidence: 99%

Immune response to RB1-regulated senescence limits radiation-induced osteosarcoma formation

Kansara¹,

Leong²,

Lin³

et al. 2013

J. Clin. Invest.

Ionizing radiation (IR) and germline mutations in the retinoblastoma tumor suppressor gene (RB1) are the strongest risk factors for developing osteosarcoma. Recapitulating the human predisposition, we found that Rb1 +/-mice exhibited accelerated development of IR-induced osteosarcoma, with a latency of 39 weeks. Initial exposure of osteoblasts to carcinogenic doses of IR in vitro and in vivo induced RB1-dependent senescence and the expression of a panel of proteins known as senescence-associated secretory phenotype (SASP), dominated by IL-6. RB1 expression closely correlated with that of the SASP cassette in human osteosarcomas, and low expression of both RB1 and the SASP genes was associated with poor prognosis. In vivo, IL-6 was required for IR-induced senescence, which elicited NKT cell infiltration and a host inflammatory response. Mice lacking IL-6 or NKT cells had accelerated development of IR-induced osteosarcomas. These data elucidate an important link between senescence, which is a cell-autonomous tumor suppressor response, and the activation of host-dependent cancer immunosurveillance. Our findings indicate that overcoming the immune response to senescence is a rate-limiting step in the formation of IR-induced osteosarcoma.

“…About 20% of patients present visible metastases with imaging at diagnosis and about 25% patients have metastases during the course of treatment. 1 Once the metastases, especially pulmonary metastases, occur it is difficult to treat them due to their poor prognosis. Currently, the characteristics of high metastasis in osteosarcoma cell lines remain unclear.…”

mentioning

confidence: 99%

Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma

Shen

Shen²,

Zheng³

et al. 2009

CIM

Clin Invest Med 2009; 32 (2): E180-E188. AbstractPurpose: To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients. Methods: Fluorescent quantitative real-time PCR was applied to study the mRNA levels of Ezrin, CD44 and Six1 genes in 32 osteosarcoma patient samples and 10 adjacent normal tissues and MG63 osteosarcoma cell lines. The analysis of relationships between pulmonary metastasis and overall survival time were carried out based on the clinical data. Results: mRNA levels of Ezrin and Six1 genes in osteosarcoma tissues were higher than those in adjacent normal tissues (P=0.015, 0.025). The mRNA levels of Ezrin, CD44 and Six1 genes were closely correlated with Enneking GTM clinical staging, while no correlations were demonstrated between the mRNA level of these genes with sex, age, location or pathological types. In addition, we demonstrated that the high mRNA level of Ezrin gene was related to shorter lung metastasis-free and overall survival time of the Chinese patients with osteosarcoma (P<0.001). Conclusion: Our data suggest that Ezrin, but not CD44 and Six1, could be a prognostic factor and a predictor of potential lung metastasis in osteosarcoma. Further large sample studies need to be done to confirm the potential value of Ezrin as a new therapeutic target.Osteosarcoma is the most common malignant primary bone tumour with high capacity of distant metastasis.Lungs and bones are the common sites for metastases. About 20% of patients present visible metastases with imaging at diagnosis and about 25% patients have metastases during the course of treatment. 1 Once the metastases, especially pulmonary metastases, occur it is difficult to treat them due to their poor prognosis. Currently, the characteristics of high metastasis in osteosarcoma cell lines remain unclear. Therefore, it is necessary to discover new indicators to assess the metastasis and prognosis in clinic.Recent studies have shown that ERM protein family members (Ezrin, Radixin and Moesin) play vital roles in the occurrence and progression of tumours. They can regulate cell activities in adhesion, migration and penetration and act as the link of cell membranes to cytoskeleton. 2-4 CD44, a cell adhesion molecule, was shown to play an important role in the process of invasion and metastasis of tumour cells, while the investigators found that Ezrin might have a synergistic effect with CD44 on the progression of tumours. 3 Thus, the prognosis of sub-group with CD44 and Ezrin high expression should be analyzed and discussed. Homology domain transcription factor Six1, a material needed in the development of normal cells is often abnormal in the process of tumour occur-CLINCAL REPORT