Introduction

The expression of PD-L1 and the intensity of the signal are significantly correlated with the histological grade according to the WHO 2010 classification. The present invention refers to a new use of the PD-L1 protein as a tumor marker for neuroendocrine neoplasms (NEN). It has been seen that in NENs there is a significant correlation between the expression of PD-L1 and grading; PD-L1 positivity rate and signal intensity are directly correlated with the increase in grade from G1 to G3.

Technical features

According to the present invention, NEN G3 are characterized by a high expression of the PD-L1 marker protein both in tumor cells and in the peri and intra tumor inflammatory infiltrate. Therefore, based on these observations, pharmacological approaches using anti-PD-1 antibodies may become the most appropriate choice for the treatment of cases of NEN G3, currently burdened with a worse prognosis. In fact, in the presence of a tumor, the PD-L1 binding to PD-1 (programmed death protein 1) causes a sequence of inhibitory signals, which inhibits the proliferation of CD8 + T cells, thus blocking the anti-tumor immune response and thus promoting growth. tumor and metastatic dissemination. Immunotherapy with inhibitors of immune check-point molecules (anti-PD-1 and anti-PD-L1 antibodies) is emerging as an important tool in the treatment of various cancers, with the achievement of a potentially lasting clinical benefit, in a good part of the patients treated and who were found to be non-responders to conventional chemotherapy treatments.

Possible Applications

• Improved classification of NEN G3, based on the level of expression of the protein;
• The use of PD-L1 as a tumor marker for NEN G3 gastrointestinal neuroendocrine neoplasms could have crucial therapeutic implications, allowing for more efficient pharmacological strategies and targeted and personalized targeted therapy.

Advantages

• Production of drugs using anti-PD-1 antibodies may become the most appropriate choice for the treatment of cases of NEN G3, currently burdened by a worse prognosis;
• Extend immunological therapy to NENs, a technique not yet used for this type of cancer.