A rare and still very difficult cancer to cure. A study opens the way to understanding the factors involved in prognosis and the possibility of studying effective immunotherapies
A rare and subtle tumor, because it does not give initial symptoms and is thus often recognized when it is at an advanced stage and difficult to cure. Cholangiocarcinoma is a malignant neoplasm that originates from the rapid and uncontrolled proliferation of cholangiocytes, the cells that make up the walls of the bile ducts. It mainly affects men and in particular after the age of 70 and in Italy every year there are about 5,400 new cases: unfortunately due to late diagnosis and resistance to many therapies (even if new effective treatments have recently arrived), the prognosis in many cases still severe today. In a study recently published in the scientific journal Journal of Hepatology, a group of Italian researchers identified the immune mechanisms linked to a worse outcome for patients with intrahepatic cholangiocarcinoma, thus paving the way for the development of targeted therapies.
A new scorer
Before this study it was not known which types of immune cells were found inside the tumor mass (immune infiltrate) of patients, which mechanisms regulated the immune response in intrahepatic cholangiocarcinoma and if these could be modified by medical cancer therapy – explains Enrico. Lugli, head of the Translational Immunology Laboratory of the Irccs Humanitas Clinical Institute in Milan, author of the research -. With our study, using technologies to analyze every single cell within the tumor, we were able to characterize the tumor infiltrate in liver samples of 25 patients undergoing liver resection surgery, comparing them with control tissues taken from healthy portions of the liver. We have seen that the immune response is inhibited. In particular, some cells of the immune system, including CD4-T-regulatory cells, usually involved in the prevention of an excessive inflammatory response, are recruited by the tumor and thus block the immune response. Furthermore, the tumor microenvironment makes these cells hyperactive: continuously stimulated to respond to inflammation, CD4 + generates a “state of tolerance” that the tumor exploits in order to inhibit the antitumor response of the immune system. from a protein, MEOX1, a transcription factor associated with a worse prognosis and higher mortality in patients in whom this protein is expressed at high levels. MEOX1 is particularly important because it regulates the expression of dozens of genes involved in maintaining cellular identity in tumors.
Future developments
With this study we were able to describe, but also to demonstrate, an immune mechanism associated with patient survival – concludes the study’s lead co-author, Ana Lleo De Nalda, hepatologist and head of the Hepatobiliary Immunopathology laboratory, director of the School of Specialization in Medicine Internal of Humanitas University -. An important data to establish the type of immunotherapy that can effectively block the development of cancer cells in patients. Given the role of T cells in the suppression of the immune response in intrahepatic cholangiocarcinoma, the hypothesis formulated by researchers that it will be possible to propose combined only immunotherapy or chemotherapy is used, but also a depletion (inhibition) of regulatory CD4 T cells. Promising data on the efficacy of chemotherapy-associated immunotherapy were confirmed in a phase III randomized international study.
August 19, 2022 (change August 19, 2022 | 09:42)
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