NEW PROGNOSTIC AND TERANOSTIC MARKERS FOR ONCOIMMUNOLOGY
The claims of the invention refer to molecular markers predictive of response to immunotherapy to assess whether a patient is responsive or resistant to immunotherapeutic treatments by defining an immunogenic or immunosuppressive tumor microenvironment. The main objective is to identify reliable biomarkers of response (not available to date) capable of orienting therapies in order to extend the benefits of treatment to a large number of patients.
The method defines an immunogenic/immunosuppressive microenvironment by evaluating the expression of the hMENA isoforms of the actin cytoskeleton regulatory protein (hMENA11a and hMENΔv6), both in tumor cells and in the stroma. The method also provides for the analysis of the stromal expression of extracellular matrix proteins with reference to fibronectin1 and the presence/spatial distribution of immune system cells (CD3-CD20-CD4-CD8) also organized in tertiary lymphoid structures (TLS). The tumor microenvironment makes it possible to distinguish patients into responsive or resistant to different therapies. The study is supported by molecular biology experiments such as:
- Expression of hMENA11a correlates with the presence of tertiary lymphoid structures (TLS) in the tumor area (AT) and low levels of stromal fibronectin in early stage NSCLC patients;
- Silencing of hMENA11a induces an increase in the PD-L1 ligand at the protein level on the membrane and in miRNA in lung cancer cells and increases the induction of PD-L1 mediated by IFNγ;
- Expression of hMENA11a correlates inversely with the expression of PD-L1 in NSCLC positive lymph nodes (N +).
- Stratification of cancer patients on the basis of their “tumor immune microenvironment” as a predictor of response to immunotherapeutic treatments.
- Simple, inexpensive and easy to perform prognostic/teranostic assay in each unit of pathological anatomy;
- Interest in pharmaceutical companies that produce immunotherapy drugs for solid tumors;
- Method applicable to different solid tumors: lung cancer, head neck, kidney, melanoma, etc