In the treatment of cancer by immunotherapy, researchers have studied how killer lymphocytes gain access to tumors to destroy them. Certain blood vessels have been identified as serving exclusively to convey them and their greater proportion is associated with a greater number of killer lymphocytes. The effectiveness of immunotherapy is thereby improved in eradicating cancerous cells.
You will also be interested
[EN VIDÉO] Cancer: better understanding tumors to better fight them Futura-Sciences traveled to the Cancer Research Center in Marseille to understand the first steps needed in the fight against cancer. From the molecular deregulation of cells to the diagnosis of the severity of the tumour.
L’immunotherapya therapeutic strategy aimed at increasing the activity of immune system to recognize and destroy cancer cells, has revolutionized the treatment of Cancer over the past ten years. Better understand how this works therapeutic approachand in particular how killer lymphocytes access to tumors during immunotherapy, could make it possible to improve the efficacy of treatments. The team of Jean-Philippe Girard, Inserm research director at the Institute of Pharmacology and Structural Biology (CNRS/Toulouse III University – Paul Sabatier), in collaboration with Gustave Roussy, has just discovered the essential role in this process of particular blood vessels, called HEV vessels associated with tumours.
Scientists have succeeded in filming for the first time the lymphocytes sneaking through the wall of the vessels HEV to enter tumors. In addition, researchers have shown in animal models that increasing the proportion of HEV vessels in a tumor improves the efficacy of immunotherapy and leads to tumor elimination.
Finally, they found that the probability of recovery of patients with melanoma metastatic (skin cancer) and treated with immunotherapy is increased when large numbers of HEV vessels are present in tumors. The results of this study, funded by Fondation ARC, FRM, INCa, ANR and Labex Toucan, are published in the journal Cancer-Cell of February 3, 20221.
Immunotherapy with therapeutic antibodies represents a true revolution for the treatment of cancer. In particular, it can cure some patients with metastatic melanoma (skin cancer), who were once doomed. Unfortunately, immunotherapy does not work for all patients or for all cancers. A better understanding of the mode of action of the treatment could make it possible to improve it and make it effective in a greater number of patients.
The royal road to enter the tumor
“killer lymphocytes”, white blood cells present in the blood, are capable of eliminating cancer cells. It is essential that a large number of these killer cells can access tumors in order to defend the body against cancer. The Toulouse team lifts the veil on the mechanisms that allow killer lymphocytes to penetrate tumors to destroy them, either spontaneously or following treatment by immunotherapy with anti-PD-1 plus anti-CTLA- 4.
For the first time, they were thus able to visualize live and in real time the lymphocytes in the process of sneaking through the wall of the HEV vessels.
Scientists have discovered that HEV vessels – for High Endothelial Vein – very special blood vessels, constitute the gate of major entry of lymphocytes into tumours. Using sophisticated microscopy techniques, the researchers were able to film the passage of lymphocytes from the blood to the tumor in animal models. For the first time, they were thus able to visualize live and in real time the lymphocytes in the process of sneaking through the wall of the HEV vessels in order to access the cancer cells present in the tumor.
” We thought that HEV vessels played an important role for lymphocyte entry into the tumor, but we were surprised to find that they were the almost exclusive entry point. “, emphasizes Jean-Philippe Girard, Inserm research director, last author of the study.
The researchers then observed in their models that the presence of a large number of killer lymphocytes in tumors is associated with the presence of a large number of HEV vessels. In addition, they provided proof of concept that increasing the proportion of HEV vessels in a tumor improves the efficacy of anti-PD-1 plus anti-CTLA-4 immunotherapy and leads to tumor elimination.
Improved diagnosis and therapeutic approach
Finally, in collaboration with Caroline Robert’s team at Gustave Roussy – also team leader in Inserm unit U981 – the scientists looked at patients with metastatic melanoma. They found that the presence of a large number of HEV vessels in tumors is associated with a better response to anti-PD-1 plus anti-CTLA-4 immunotherapy.
The next step for researchers will be to develop treatments aimed at increasing the proportion of HEV vessels in tumors, in order to improve the effectiveness of immunotherapy, allowing massive recruitment of killer lymphocytes to eradicate cancer cells. “ Our work could allow in the longer term to improve immunotherapy treatment for patients with metastatic melanoma and other types of tumors solid. They also have prognostic implications, with clinicians now able to look at HEV vessels to predict a patient’s response to immunotherapy. concludes Jean-Philippe Girard.
Interested in what you just read?