Immunoregulation represents a booming field of biomaterial design. The unique physical and chemical properties of biomaterials offer tremendous opportunities for development. Each of their parameters exerts immunogenic effects at the immune system, cellular, and molecular levels. Herein, the perspective summarizes the interaction of biomaterials with immune cells and the underlying mechanisms to control immunoregulation in a top-down manner, providing solid inspiration for biomedical applications of immunologically effective biomaterials.
The overall survival rate of patients with osteosarcoma has remained stagnant at 15–30% for several decades. Although immunotherapy has revolutionized the oncology field, largely attributed to the success of immune-checkpoint blockade, the durability and efficacy of anti-PD1 (programmed cell death protein 1) mAb vary across different malignancies. Among the major reasons for tumor resistance to this immune checkpoint therapy is the absence of tumor-infiltrating cytotoxic T lymphocytes. However, the presence of intratumor exhausted PD1 hi T cells also contributes to insensitivity to anti-PD1 treatment. In this study, we established the osteosarcoma mouse tumor model resistant to anti-PD1 mAb that harbored PD1 hi T cells. Furthermore, flow cytometry analysis of tumor infiltrating leukocytes after treatment was used as a screening platform to identify agents that could re-sensitize T cells to anti-PD1 mAb. Results showed that anti-CD40 mAb treatment converted PD1 hi T cells to PD1 lo T cells, reversing phenotypic T cell exhaustion and sensitizing anti-PD1 refractory tumors to respond to anti-PD1 mAb. Results also showed that intratumor Treg presented with a less activated and attenuated suppressive phenotype after anti-CD40 mAb treatment. Our study provides proof of concept to systematically identify immune conditioning agents, which are able to convert PD1 hi T cells to PD1 lo T cells, with clinical implications in the treatment against refractory osteosarcoma to anti-PD1 mAb.
Accumulating evidence has suggested that concentrations of blood-based circulating micro-ribonucleic acids (microRNAs, miRNAs) in breast tumor patients are significantly higher/lower than that in normal individuals, indicating that circulating miRNAs may serve as novel blood-based biomarkers for breast tumor. However, the results of previous studies on this issue have been inconclusive. Therefore, we perform a meta-analysis to determine whether aberrant miRNA expression can be used as molecular markers in blood for the diagnosis of breast tumor. PubMed and other databases were searched to identify eligible studies. The sensitivity and specificity were used to plot the summary receiver operator characteristic curve and calculate the area under the curve (AUC). Finally, 15 articles with a total of 1,428 breast tumor patients and 952 healthy individuals were involved. The summary estimates revealed that the pooled sensitivity was 76 % with 95 % confidence interval (CI) of 67-83 %; the specificity was 87 % with 95 % CI of 77-93 %; the PLR was 5.9 with 95 % CI of 3.3-10.4; the NLR was 0.28 with 95 % CI of 0.20-0.39; the DOR was 21 with 95 % CI of 10-44; and the AUC was 0.88 with 95 % CI of 0.84-0.90. The most noteworthy is that multiple-miRNA assay displayed a better diagnostic performance than single-miRNA assay. In summary, the results of the present meta-analysis suggested that blood-based miRNAs may serve as novel molecular biomarkers for breast tumor, with a relative high level of accuracy, especially based on multiple-miRNA assay. Further large-scale prospective studies are necessary to validate their potential applicability for breast tumor prognosis, treatment, and surveillance.
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