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The research was led by George Coukos, Melita Irving and Fernanda Herrera of the Ludwig Institute for Cancer Research and was published in Cancer Discovery
Many types of tumors have almost no tumor-infiltrating T lymphocytes (TILs), which are immune cells necessary for the anti-cancer response
"We came up with the idea that this level of radiation will not kill the tumor cells, but still exert enough pressure to make it signal the immune system to come to me because there is a problem here," Herrera Say
But the researchers reasoned that generating an anti-tumor response requires a multi-pronged strategy
"We began to analyze what happened to the microenvironment of mouse ovarian tumors? If low-dose radiation is used, it can show that the expression of drug targets has increased significantly.
After studying several drug combinations, they selected four for mouse research: an existing antibody that can stimulate the receptor CD40 on dendritic cells and increase their activity; low-dose chemotherapy; Cyclophosphamide, known to inhibit treg; and a combination of anti-ctla-4 and anti-pd-1 immunotherapy, they can mobilize T cells to attack tumors
At the same time, the researchers began to design a clinical study on this method and modified the research protocol based on the results of the mouse study
The clinical study of the program included 8 patients with metastatic prostate cancer, ovarian cancer, and gastrointestinal cancer.
One patient developed a heart disease related to immunotherapy, so the trial was cancelled
"Reproduce the human studies we found that the mice"
The analysis of reactive mouse tumors shows that TILs have the most negative effect on tumor destruction, not the typical CD8 killer T cells that destroy diseased cells
"Our research really shows that low-dose radiation can make tumors that have not responded to immunotherapy before, and adaptive immunity and innate immunity need to work together to control the tumor
The second part of the clinical study continues, but researchers are already exploring why some tumors escape treatment
"We are a bit like detectives in the tumor microenvironment, observing what one cell can do and the other cannot do.
Journal Reference :
Fernanda G Herrera, Catherine Ronet, Maria Ochoa de Olza, David Barras, Isaac Crespo, Massimo Andreatta, Jesus Corria-Osorio, Aodrenn Spill, Fabrizio Benedetti, Raphael Genolet, Angela Orcurto, Martina Imbimbo, Eleonora Dominivark Rdrigo Berthold, Apostolos Sarivalasis, Khalil Zaman, Rafael Duran, Clarisse Dromain, John Prior, Niklaus Schaefer, Jean Bourhis, Georgia Dimopoulou, Zoi Tsourti, Marius Messemaker, Thomas Smith, Sarah E Warren, Periklis Foukas, Sylet, Rusakiewicz, Mika Pittvie, Rusakiewicz, Zimmermann, Christine Sempoux, Urania Dafni, Alexandre Harari, Lana E Kandalaft, Santiago J Carmona, Denarda Dangaj Laniti, Melita Irving, George Coukos.