br Furthermore the pathway analysis of the pre and post
Furthermore, the pathway analysis of the pre- and post-treatment differential gene expression testing results using GSEA revealed over-representation of overlap with gene sets from the immunologic sig-natures gene set collection. Indicative overlapping gene sets include 4 sets specifically involving T regulatory lymphocytes, as well as gene sets that are upregulated in CD4 thymocytes versus thymic stromal cells, the set of upregulated genes after interleukin-4 treatment of macrophages and monocytes, genes downregulated in a comparison of untreated CD8 lymphocytes versus CD8 lymphocytes treated with leukocyte costimulatory blockade antibodies, and genes down-regulated in mature natural killer (NK) Iberiotoxin versus intermediate NK cells. These findings highlight that a significant part of the changes that happen in the tumor microenvironment after the trial treatment are immune-related. Our results suggest that the combination of AMP-224 with a low dose of cyclophosphamide and SBRT at the dose and schedule administered in this trial exhibits some effect on antitumor immunity modulation. However, the magnitude of this immunomodulatory effect does not result in clinical benefit.
The results of this trial showed that the combination of the PD-1 antagonist AMP-224 with low-dose cyclophosphamide and SBRT in patients with mCRC is safe but did not provide evidence that is feasible or that it possesses antitumor efficacy. Further exploration of alternative combinations of AMP-224 is warranted.
Clinical Practice Points
In this study we investigated the benefit of using AMP-224 immunotherapy with radiation in 15 patients with mCRC.
No objective response was observed although 20% of the pa-tients had stable disease.
AMP-224 in combination with SBRT and low-dose cyclophos-phamide was well tolerated, however, no significant clinical benefit was observed in patients with mCRC.
The authors’ work is supported by the intramural program of the National Institutes of Health ZIA BC 011343.
The authors have stated that primary root have no conflicts of interest. Charalampos S. Floudas et al
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