How to play chess with sickness. A scheme of combinations (of drugs) to circumvent resistance to therapies, so as to make the neuroendocrine tumor of the pancreas again sensitive to attacks by the immune system. This is the idea behind the study published on Immunity by the group of researchers led by Douglas Hanahan of the Ecole Polytechnique Fédérale de Lausanne, which has just tested a strategy for two different immunotherapy treatments. The research for now concerns animal models, but it is an important testing ground for imagining carrying out studies also in the clinical setting.
What are neuroendocrine tumors
Neuroendocrine tumors (NET, from Neuro-endocrine Tumors) owe their name to the fact that they present both the characteristics of neurons and glandular cells, which secrete hormones. They represent a rare but increasing disease. It is estimated that approximately 5 newly diagnosed patients with neuroendocrine tumors per 100,000 population each year. We are therefore talking about tumors with a low incidence but, given their slow growth and the possibility of living with the disease for a long time, their prevalence is high. The most frequent Nets are those affecting the gastro-entero-pancreatic tract, such as the one that affected about a year ago Fedez.
Neuroendocrine tumor of the pancreas: this is what Fedez’s disease is
by Irma D’Aria, Tiziana Moriconi
Immunotherapy: the problem of resistance
The field of immunotherapy has been – and still is – one of the most innovative in the fight against cancer. The idea that the immune system could be used to fight cancer earned James P. Allison and Tasuku Honjo the Nobel Prize in 2018. But even though it is now officially recognized as the fourth pillar in the fight against cancer – after surgery, radiotherapy and chemotherapy – immunotherapy also suffers from some limitations. Two above all, the experts remind: in about half of the cases the therapies don’t work or work for a while, after which resistance develops, i.e. they stop having an effect.
Tumors, the secret to improving immunotherapy is in the genes
by Sara Carmignani
The combo move
The idea that the scientists had was to overcome the resistance developed by a particular type of tumor, the neuroendocrine tumor of the pancreas by acting on three different fronts. First of all, they used a dual action engineered protein: one part binds and inhibits the PD-1 molecule (expressed on the cells of the immune system, where it acts as a brake) and one part directly stimulates the T lymphocytes that attack the tumor (the protein , called PD1-IL2v, is therefore, technically, a bispecific immunocytokine and is under investigation). The researchers also associated it with an anti-PD-L1 drug, an immune checkpoint inhibitor (PD-L1 is a protein expressed in high quantities in some cancer cells, which helps to turn off the immune system responses against cancer), already used in the clinic.
Liver cancer, identified a molecular signature that predicts the effectiveness of immunotherapy
by Valentina Guglielmo
Next step: human trials
Results in animal models show an improvement in response. How? In detail, the molecule with dual specificity would be able to expand the proportion of T lymphocytes in the tumor, explain the authors. The anti PD-L1, on the other hand, manages to sensitize the diseased cells by acting on the macrophages associated with the tumor, reprogramming them. In fact, it is as if the tumor environment, with immunosuppressive activity before treatment, were modified, developing a pro-inflammatory profile that facilitates the attack by the immune system. What has been observed, the experts conclude, provides the basis for continuing studies in the field, with clinical trials that combine these two treatments for tumors resistant to immunotherapy.