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Updated: Aug 31, 2025
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
A novel anti-CD47-targeted blockade promotes immune activation in human soft tissue sarcoma but does not potentiate
Andrej Ozaniak1, Jitka Smetanova2, Robin Bartolini3
1Third Department of Surgery, First Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, 150 06, Prague, Czech Republic.
Purpose:
The treatment options for metastatic soft tissue sarcomas (STSs) are limited. In most cases, immunotherapy with immune checkpoint inhibitors has not been successful so far. Macrophages dominate the immune landscape of STSs; thus, combinatorial strategies aiming at both tumor-infiltrating lymphocytes and macrophages may represent a particularly relevant treatment approach for metastatic or recurrent STSs.
Methods:
In this cohort study, 66 patients who underwent surgery for STSs were enrolled. Tumor cells and tumor-infiltrating immune cells were analyzed using flow cytometry and immunohistochemistry. In cell suspensions obtained from surgical resections, human T cells were activated by superparamagnetic polymer beads and cultured at a concentration of 0.3 × 106/µl in the absence or presence of therapeutic monoclonal antibodies (anti-PD-1, anti-CD47, and anti-PD-1 + anti-CD47). Supernatants from cell suspensions were analyzed using multiplex Luminex cytokine bead-based immunoassays.
Results:
The most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma which also displayed high expression of CD47 in the tumor microenvironment. Both anti-PD-1 and anti-CD47 therapies drastically increased the production of pro-inflammatory cytokines in the tumor microenvironment of STSs, but co-administration of both agents did not further increase cytokine secretion. Furthermore, all patient samples treated with a combination of both anti-PD-1 and anti-CD47 antibodies showed a dramatic reduction in cytokine secretion.
Conclusion:
Our findings suggest that anti-PD-1 and anti-CD47 therapies do not enhance each other, and the combined application of anti-PD-1 and anti-CD47 agents in vitro limits rather than potentiates their efficacy.
Insights
Combination immunotherapy with anti-PD-1 and anti-CD47 antibodies showed limited efficacy in soft tissue sarcomas (STSs). In vitro studies revealed that combining these immune checkpoint inhibitors did not enhance anti-tumor cytokine production and may reduce their overall effectiveness.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Metastatic soft tissue sarcomas (STSs) have limited treatment options.
- Immunotherapy using immune checkpoint inhibitors has shown limited success in STSs.
- Macrophages are prevalent in the STS immune microenvironment, suggesting combined therapeutic strategies targeting lymphocytes and macrophages.
Purpose of the Study:
- To investigate the efficacy of combining anti-PD-1 and anti-CD47 therapies in treating soft tissue sarcomas.
- To evaluate the impact of these combined therapies on the tumor immune microenvironment and cytokine production.
Main Methods:
- A cohort study involving 66 patients with surgically resected STSs.
- Analysis of tumor cells and infiltrating immune cells using flow cytometry and immunohistochemistry.
- In vitro culture of T cells with therapeutic monoclonal antibodies (anti-PD-1, anti-CD47, or both) and analysis of cytokine secretion via Luminex assays.
Main Results:
- Anti-CD47 therapy showed a notable response in a pleomorphic sarcoma with high CD47 expression.
- Both anti-PD-1 and anti-CD47 monotherapies increased pro-inflammatory cytokine production.
- Combined anti-PD-1 and anti-CD47 treatment did not enhance cytokine secretion and, in some cases, led to a reduction.
Conclusions:
- Anti-PD-1 and anti-CD47 therapies do not appear to enhance each other's efficacy in STSs.
- In vitro combination of anti-PD-1 and anti-CD47 antibodies may limit their therapeutic potential.
