Ricerc@Sapienza

Understanding the principles of cancer immune evasion is essential to determine new methods to elicit a strong, specific, and durable anti-tumor immune response.
Exploring the cancer immune tolerance phenomenon looking at a similar system, such as immune tolerance towards a haploidentical fetus, takes another approach to understand the complex immune regulation in tumorigenesis. The maternal IS must effectively balance tolerance to paternal antigens while continuing to protect the mother from infections.
One of the most impacting discoveries of the new Millennium is that maternal peripheral blood contains cell-free DNA (cf-DNA) sequences derived from the fetus/trophoblast complex. This observation has led to the development and large spread of a non-invasive prenatal test (NIPT) to detect specific fetal chromosomal anomalies through the sampling of a low quantity of maternal blood. Interestingly, by late pregnancy the concentration of cf-DNA significantly increases. A new hypothesis recently arose suggests that the increase in cf-DNA at term could activate TLRs on maternal cells, which leads to the breakage of immune tolerance, the activation of innate immune cells, and finally the labor onset.
This mechanism might also be applicable to reactivating anti-tumor immunity in cancer patients.
Aim of this project is to assess the genetic/epigenetic profile and the immunomodulatory effects of cancer-specific cell-free DNA (cs-cf-DNA) detected in HGSOC patients¿ blood. In particular, we propose to:
- identify cs-cf-DNA sequences from high-grade serous ovarian cancer (HGSOC) patients¿ plasma;
- quantify their concentrations;
- associating them with tumor stage, grading, response to treatments and survival;
- test the immunomodulatory effect of cs-cf-DNAs by in vitro immune-assays on cancer patients¿ plasma.