Immune profiles of desmoplastic small round cell tumor and synovial sarcoma suggest different immunotherapeutic susceptibility upfront compared to relapse specimens

Wedekind, Mary Frances; Haworth, Kellie B.; Arnold, Michael A.; Stanek, Joseph; Lee, Dean A.; Cripe, Timothy P.

doi:10.1002/pbc.27313

Cited by 13 publications

(14 citation statements)

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“…Earlier it has been demonstrated by Wedekind M.F. et al (2018) that initially low levels of cytotoxic T-lymphocytes presence in infiltrates of synovial and desmoplastic sarcoma have been further reduced with disease progression [3]. The work shows the growth in dynamics of NK cell level in these tumor histotypes.…”

Section: Resultsmentioning

confidence: 58%

Clinical and immunological charactereistics...

2020

Bioinformatics of Genome Regulation and Structure/ Systems Biology

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The search of new predictor markers for disease outcomes and treatment efficacy is crucial for metastatic sarcoma, where prognosis is unfavourable and the choice of chemotherapy is limited. In our work we present the results of in vitro clonogenic abilities study of tumor cells connection with immunological parameters of peripheral blood and survival rate of patients with metastatic soft tissue sarcomas and bones sarcomas (STBS). Keywordssarcoma, clonogenic potential, immunological indicatorsMotivation and aim Today the state of the immune cellular link is widely discussed as a predictor of the response to immunotherapy. It is undoubted interest for sarcoma, where the effectiveness of chemotherapy is low and prognosis is unfavorable, especially in the development of metastatic disease [1]. Genetic, histological and morphological diversity of different clones inside the tumor and peculiarities of their relations with the patient's immune system mainly presented on tumors models with epithelial origin. Tumours with mesenchymal origin, such as STBS, haven't been sufficiently studied in this regard. Cloning with the limiting dilution method demonstrates the presence of self-regulating tumor cells in the population and can serve as an independent predictor of adverse prognosis.

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Section: Resultsmentioning

confidence: 58%

Clinical and immunological charactereistics...

2020

Bioinformatics of Genome Regulation and Structure/ Systems Biology

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“…SS has a low level of tumor infiltrating T cells (TIL). [84][85][86][87] While in some inflammatory tumors like melanoma TIL are a marker for better prognosis, 85 86 there is evidence suggesting that higher levels of CD8+ lymphocytes in the TME of SS might lead to worse metastasis free survival. 88 Wedekind, et al in particular found that recurrent or metastatic tumors were less likely to have high TIL infiltration, suggesting that the tumor may acquire changes allowing it to evade the immune system.…”

Section: Ss Microenvironmentmentioning

confidence: 99%

“… 88 Wedekind, et al in particular found that recurrent or metastatic tumors were less likely to have high TIL infiltration, suggesting that the tumor may acquire changes allowing it to evade the immune system. 87 One potential clinical consequence of this finding is that immune modulating treatment earlier in the patient’s course of disease might be of greater benefit than waiting for recurrence. 87 PD-L1, PD-1, and CD8+ T cells are enriched at the perimeter of SS tumor, but relatively low inside the tumor.…”

Section: Ss Microenvironmentmentioning

confidence: 99%

“… 87 One potential clinical consequence of this finding is that immune modulating treatment earlier in the patient’s course of disease might be of greater benefit than waiting for recurrence. 87 PD-L1, PD-1, and CD8+ T cells are enriched at the perimeter of SS tumor, but relatively low inside the tumor. 89 NY-ESO-1 expression levels are not correlated to CD8+ lymphocyte density in the tumor, indicating that the presence of CTAs in the tumor cells are not enough to stimulate endogenous cytotoxic T-cells into the tumor.…”

Section: Ss Microenvironmentmentioning

confidence: 99%

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Targeting cancer testis antigens in synovial sarcoma

Mitchell

Pollack

Wagner

2021

J Immunother Cancer

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Synovial sarcoma (SS) is a rare cancer that disproportionately affects children and young adults. Cancer testis antigens (CTAs) are proteins that are expressed early in embryonic development, but generally not expressed in normal tissue. They are aberrantly expressed in many different cancer types and are an attractive therapeutic target for immunotherapies. CTAs are expressed at high levels in SS. This high level of CTA expression makes SS an ideal cancer for treatment strategies aimed at harnessing the immune system to recognize aberrant CTA expression and fight against the cancer. Pivotal clinical trials are now underway, with the potential to dramatically alter the landscape of SS management and treatment from current standards of care. In this review, we describe the rationale for targeting CTAs in SS with a focus on NY-ESO-1 and MAGE-A4, the current state of vaccine and T-cell receptor-based therapies, and consider emerging opportunities for future development.

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“…Ewing sarcoma [57], chondrosarcoma [64], pediatric [65] and adult [29,36] alveolar and embryonal rhabdomyosarcoma, and synovial sarcoma [29,34,41,58,66] show little to no PD-L1 expression on malignant cells. Studies on DDLPS and pleomorphic liposarcomas [41,64], myxofibrosarcoma [38,41], fibrosarcoma [41], desmoplastic small round cell tumor [29,66], osteosarcoma [38,58,64,67], UPS [38,64], and pleomorphic dermal sarcoma [39] report less than half the cases show PD-L1 expression on the sarcoma cells. In comparison, PD-L1 was expressed on the neoplastic cells in more than half of leiomyosarcoma [35,37,41] and giant cell tumor specimens [58].…”

Section: Pd-l1mentioning

confidence: 99%

Sarcomas: Immune biomarker expression and checkpoint inhibitor trials

Zhu

Shenasa

Nielsen

2020

Cancer Treatment Reviews

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Sarcomas are a heterogenous group of mesenchymal cancers comprising over 100 subtypes. Current chemotherapy for all but a very few subtypes has limited efficacy, resulting in 5-year relative survival rates of 16% for metastatic patients. While sarcomas have often been regarded as an "immune cold" tumor category, recent biomarker studies have confirmed a great deal of immune heterogeneity across sarcoma subtypes. Reports from the first generation of clinical trials treating sarcomas with immunotherapy demonstrate a few positive responses, supporting efforts to stratify patients to optimize response rates. This review summarizes recent advances in knowledge around immune biomarker expression in sarcomas, the potential use of new technologies to complement these study results, and clinical trials particularly of immune checkpoint inhibitor therapy in sarcomas.Each of the immune biomarkers assessed was reviewed for subtype-specific expression patterns and correlation with prognosis. Overall, there is extensive heterogeneity of immune biomarker presence across sarcoma subtypes, and no consensus on the prognostic effect of these biomarkers. New technologies such as multiplex immunohistochemistry and high plex in situ profiling may offer more insights into the sarcoma microenvironment. To date, clinical trials using immune checkpoint inhibitor monotherapy have not shown compelling clinical benefits. Combination therapy with dual checkpoint inhibitors or in combinations with other agents has yielded more promising results in dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, angiosarcoma and alveolar soft-part sarcoma. Better understanding of the sarcoma immune status through biomarkers may help decipher the reasons behind differential responses to immunotherapy.

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Immune profiles of desmoplastic small round cell tumor and synovial sarcoma suggest different immunotherapeutic susceptibility upfront compared to relapse specimens

Cited by 13 publications

References 40 publications

Clinical and immunological charactereistics...

Clinical and immunological charactereistics...

Targeting cancer testis antigens in synovial sarcoma

Sarcomas: Immune biomarker expression and checkpoint inhibitor trials

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