Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials

Groisberg, Roman; Hong, David S.; Amini, Behrang; Hess, Kenneth R.; Janků, Filip; Piha-Paul, Sarina A.; Naing, Aung; Fu, Siqing; Benjamin, Robert S.; Patel, Shreyaskumar; Somaiah, Neeta; Conley, Anthony P.; Meric‐Bernstam, Funda; Subbiah, Vivek

doi:10.1186/s40425-017-0301-y

Cited by 123 publications

(111 citation statements)

References 37 publications

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“…The dissociation in the expression of CD8 and and PD1/PD-L1 axis suggests that adenosarcoma is a less favorable target for PD1/PD-L1 checkpoint inhibitors [27] and may use an alternate immune escape mechanism. Further investigations are required to identify immunologic therapeutic targets that may affect uterine adenosarcoma or other soft tissue sarcomas [8,10,28].…”

Section: Discussionmentioning

confidence: 99%

The immune microenvironment of uterine adenosarcomas

et al. 2020

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Background: Uterine adenosarcoma (UA) is an extremely rare sarcoma subtype. There has been limited evaluation of the immune microenvironment in these tumors. The objective of this study is to examine and describe the immune infiltrate and PD-1/PD-L1 expression in UA and to correlate these changes in the tumor micro-environment with the overall survival status or the disease-free survival status (DFSS), respectively.Methods: Patients (pts) treated at our center from 1982 to 2014 with UA were identified. Fifteen cases had tumor paraffin-embedded blocks available. Immunohistochemistry studies for CD3, CD8, FOXP3, CD163, PD-1 and PD-L1 (clone 22C3) were performed. Image analysis was used to assess the density (cells/mm 2 ), except in PD-L1, where the percentage of membranous staining on tumor cells was noted.Results: Immune infiltrate analysis median (range) density in cells/mm 2 varied broadly: CD3 178 (15-802); CD8 117 (11-661); FoxP3 4.8 (0.2-82); CD163 791 (264-1861); and PD1 5 (1-65). 3 cases had rare (1%) PD-L1 tumor membranous labeling. The reports yielded that ten pts were alive, and 5 were dead. Pts who were alive had significant higher CD3 and CD8 median densities in tumors than those who were dead (p = 0.040). There was no correlation between DFSS and CD3 or CD8 median densities. Patients who had no local recurrence had significantly higher CD3 and CD8 median densities in tumors than those who had local recurrence (p = 0.040). Conclusions:In conclusion, this is the first report characterizing the presence of immune infiltrate and PD-1/PD-L1 expression in UA. CD3+ CD8+ T-cells density may be prognostic. The immune-responsiveness of UA needs to be further investigated in a larger study.

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Section: Discussionmentioning

confidence: 99%

The immune microenvironment of uterine adenosarcomas

et al. 2020

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“…Of note, other investigators have demonstrated stable disease for 33% (3/9) in patients with metastatic or unresectable GIST treated with checkpoint inhibitor-based trials. 16 Interestingly, this tumor had a low density of CD3 + T cells, which is unique for this patient given that higher levels of CD3+ infiltrates may portend a superior PFS. 17 Furthermore, while the co-localization of CD163+ and PD-L1 was expected, the expression of FOXP3 largely in the absence of CD3+ and CD4+ was surprising.…”

Section: Discussionmentioning

confidence: 85%

“…21 Because imatinib has activity against IDO in the GIST microenvironment, 22 the combination of imatinib and anti-PD1 has been investigated in murine models with promising synergy, 14 but this has been less evident in a phase I clinical trial. 16 However, PD1 is probably critical because when KIT inhibition was combined with the CTLA-4 inhibitor ipilimumab, clinical outcomes did not appear improved. 23 PD-L1 expression in GIST can be heterogenous, particularly in higher-risk tumors, further strengthening the argument for combination immunotherapy, and a trial is now ongoing at UCLA (NCT02880020) comparing single-agent nivolumab (anti-PD-1) alone or in combination with ipilimumab (anti-CTLA-4).…”

Section: Discussionmentioning

confidence: 99%

Durable tumor regression in highly refractory metastatic KIT/PDGFRA wild-type GIST following treatment with nivolumab

et al. 2020

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2020) Durable tumor regression in highly refractory metastatic KIT/PDGFRA wild-type GIST following treatment with nivolumab, OncoImmunology, 9:1, 1710064, ABSTRACTGastrointestinal stromal tumor (GIST) is a devastating disease, especially in the setting of metastasis. The natural progression of GIST has been significantly altered by the development of small molecule tyrosine kinase inhibitors (TKIs), including imatinib, sunitinib, and regorafenib, all of which are FDA approved. However, TKIs are not always well-tolerated, and the refractory disease continues to be a problem. For these reasons, alternative treatments are needed. In this report, we discuss a patient with metastatic wild-type (WT) GIST refractory to multiple TKIs, but with a durable clinical response to the antiprogrammed cell death protein 1 (PD-1) antibody, nivolumab. This report suggests that continued research evaluating checkpoint inhibitors in GIST is warranted. ARTICLE HISTORY

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“…Accumulating epidemiological data showed that the treatment for OS has remained essentially unchanged since the 1970s. e survival rates of OS patients were likewise maintained [53,54]. A more intensive understanding of the mechanisms that drive metastasis and tumor heterogeneity coupled with available and clinically annotated data sets is urgently needed in the clinic.…”

Section: Discussionmentioning

confidence: 99%

hsa_circ0021347 as a Potential Target Regulated by B7-H3 in Modulating the Malignant Characteristics of Osteosarcoma

Wang

Zhang

Kang

et al. 2019

BioMed Research International

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In our previous study, we showed that B7-H3 played crucial roles in osteosarcoma (OS) development and might serve as a negative regulator of in osteoimmunology and help tumor cells escape immune surveillance. However, little is known about B7-H3 deficiency and its corresponding circRNA alteration or their relationship with osteosarcoma progression. erefore, we established stable silencing of B7-H3 in OS cells and validated our results with western blotting and real-time PCR detection. en, we performed a circRNA array to analyze the differential expression of circRNAs between the control and B7-H3 knockdown cells. e association between target circRNA expression and the clinicopathological features of patients with OS was further analyzed. As a result, hsa_circ0021347 was selected and validated to be significantly downregulated in OS tissues and cell lines and showed a strong negative relationship with B7-H3 expression in OS. In addition, clinicopathological features showed that hsa_circ0021347 in OS tissues was negatively associated with Enneking stage and positively associated with patients' survival. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and PANTHER pathway analyses were performed to predict a network of hsa_circ0021347/miRNAs interactions to help us develop potential biomarkers for clinical diagnosis and design therapeutic strategies for OS.

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Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials

Cited by 123 publications

References 37 publications

The immune microenvironment of uterine adenosarcomas

The immune microenvironment of uterine adenosarcomas

Durable tumor regression in highly refractory metastatic KIT/PDGFRA wild-type GIST following treatment with nivolumab

hsa_circ0021347 as a Potential Target Regulated by B7-H3 in Modulating the Malignant Characteristics of Osteosarcoma

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