Role of immunotherapy in Ewing sarcoma

Morales, Erin; Olson, Michael; Iglesias, Fiorella; Dahiya, Saurabh; Luetkens, Tim; Atanackovic, Djordje

doi:10.1136/jitc-2020-000653

Cited by 50 publications

(49 citation statements)

References 202 publications

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“…Initial experience with ICIs for EwS has yielded few if any responses, though many trials are currently underway [328]. Immunotherapy for EwS must contend with certain challenges, some of which a recent review summarized as including lack of HLA class I expression in the tumor and an immunosuppressive tumor microenvironment due to the presence of myeloid-derived suppressor cells, F2 fibrocytes, and M2-like macrophages [329]. In addition to these antibody-based approaches, several cell-based immunotherapy strategies are currently investigated in clinical trials.…”

Section: Immunotargeting Of Ews Tumorsmentioning

confidence: 99%

Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives

Zöllner

Amatruda

Bauer

et al. 2021

JCM

131

114

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Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival.

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Section: Immunotargeting Of Ews Tumorsmentioning

confidence: 99%

Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives

Zöllner

Amatruda

Bauer

et al. 2021

JCM

131

114

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“…It blocks the downstream effects of the VEGF pathway in angiogenesis (21). In another research, Bevacizumab, a monoclonal antibody targeting VEGF receptor, has been tested in a phase II clinical trial (22). In our study, the VEGFA-VEGFR2 signaling pathway was active in EC and CS.…”

Section: Discussionmentioning

confidence: 54%

The Key Gene Expression Patterns and Prognostic Factors in Malignant Transformation from Enchondroma to Chondrosarcoma

Wu¹,

Huang²,

Yu³

et al. 2021

Front. Oncol.

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Enchondroma (EC) is a common benign bone tumor. It has the risk of malignant transformation to Chondrosarcoma (CS). However, the underlying mechanism is unclear. The gene expression profile of EC and CS was obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using GEO2R. We conducted the enrichment analysis and constructed the gene interaction network using the DEGs. We found that the epithelial-mesenchymal transition (EMT) and the VEGFA-VEGF2R signaling pathway were more active in CS. The CD8+ T cell immunity was enhanced in CS I. We believed that four genes (MFAP2, GOLM1, STMN1, and HN1) were poor predictors of prognosis, while two genes (CAB39L and GAB2) indicated a good prognosis. We have revealed the mechanism in the tumor progression and identified the key genes that predicted the prognosis. This study provided new ideas for the diagnosis and treatment of EC and CS.

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“…Immunotherapy, in any form, has thus far demonstrated discouraging results in bone sarcomas, including ES. Suppression of the immune response by the tumor microenvironment in ES involves different mechanisms, such as expression of myeloid-derived suppressor cells; expansion of immunosuppressive fibrocytes; low expression of human leukocyte antigens (HLAs) A, B, and C; and high expression of HLA-G, which suppresses tumor-specific T-cells [ 69 ]. Due to the limited mutational burden and low expression of programmed death ligand-1 (PD-L1), the probability of response to immune checkpoint inhibitors in monotherapy is low [ 70 , 71 ].…”

Section: Novel Systemic Treatmentsmentioning

confidence: 99%

Current Status of Management and Outcome for Patients with Ewing Sarcoma

Hesla

Papakonstantinou

Tsagozis

2021

Cancers

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Ewing sarcoma is the second most common bone sarcoma in children after osteosarcoma. It is a very aggressive malignancy for which systemic treatment has greatly improved outcome for patients with localized disease, who now see survival rates of over 70%. However, for the quarter of patients presenting with metastatic disease, survival is still dismal with less than 30% of patients surviving past 5 years. Patients with disease relapse, local or distant, face an even poorer prognosis with an event-free 5-year survival rate of only 10%. Unfortunately, Ewing sarcoma patients have not yet seen the benefit of recent years’ technical achievements such as next-generation sequencing, which have enabled researchers to study biological systems at a level never seen before. In spite of large multinational studies, treatment of Ewing sarcoma relies entirely on chemotherapeutic agents that have been largely unchanged for decades. As many promising modern therapies, including monoclonal antibodies, small molecules, and immunotherapy, have been disappointing to date, there is no clear candidate as to which drug should be investigated in the next large-scale clinical trial. However, the mechanisms driving tumor development in Ewing sarcoma are slowly unfolding. New entities of Ewing-like tumors, with fusion transcripts that are related to the oncogenic EWSR1-FLI1 fusion seen in the majority of Ewing tumors, are being mapped. These tumors, although sharing much of the same morphologic features as classic Ewing sarcoma, behave differently and may require a different treatment. There are also controversies regarding local treatment of Ewing sarcoma. The radiosensitive nature of the disease and the tendency for Ewing sarcoma to arise in the axial skeleton make local treatment very challenging. Surgical treatment and radiotherapy have their pros and cons, which may give rise to different treatment strategies in different centers around the world. This review article discusses some of these controversies and reproduces the highlights from recent publications with regard to diagnostics, systemic treatment, and surgical treatment of Ewing sarcoma.

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Role of immunotherapy in Ewing sarcoma

Cited by 50 publications

References 202 publications

Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives

Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives

The Key Gene Expression Patterns and Prognostic Factors in Malignant Transformation from Enchondroma to Chondrosarcoma

Current Status of Management and Outcome for Patients with Ewing Sarcoma

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