Thursday, 01 August 2019 16:45

Tumor cells express proteins on their surface capable of modifying cytotoxic cells metabolism

Cancer immunotherapy has become an effective strategy of the antioncological arsenal, but it only works in certain types of cancer and in a limited number of patients. Although the immune system can recognise and eliminate tumor cells, tumors have evasion mechanisms to prevent it. One of them is the expression of PD-L1 protein on the surface of tumors, which blocks the antitumor capacity of cytotoxic CD8 lymphocytes through mechanisms that are still poorly understood. 

A group of researchers led by Santos Mañes from the National Center for Biotechnology (CNB-CSIC), has identified PD-L1 mechanism to inactivate cytotoxic cells by altering the mitochondria and reprogramming the cell metabolism and publish their results in the Journal for Immunotherapy of Cancer.

"We know that if we block the interaction between PD-L1 and the immune system, tumors can be more effectively attacked. This is why numerous antibody-based therapies that block these interactions are currently being tested, although the exact mechanism of evasion of the immune system by tumors is unknown” explains Jesús Ogando, researcher at the National Biotechnology Center. “Thanks to this work, we understand how tumors modify the structure of mitochondrial crests and reprogram cellular metabolism towards the use of fatty acids as the main source of energy. These changes block cytotoxic responses on cancer cells ”adds Ogando. 

Rosa Ana Lacalle, co-director of the research, summarises: "This finding opens the door to design strategies to restore cytotoxic function and increase the antitumor immune response." 

This work has been carried out thanks to the funding of the Merck-Health Foundation, the Ministry of Science, Innovation and Universities and the Community of Madrid and with the collaboration of researchers from different CSIC centers; the Center for Biomedical Research in the Network of Rare Diseases, the Andalusian Center for Bioinformatics Studies, in Seville; the Center for Genomic Regulation of Barcelona, ​​the Autonomous University of Madrid and the Pompeu Fabra University in Barcelona.

Jesús Ogando, María Eugenia Sáez, Javier Santos, Cristina Nuevo-Tapioles, Marta Gut, Anna Esteve-Codina, Simon Heath, Antonio González-Pérez, José M. Cuezva, Rosa Ana Lacalle y Santos Mañes. PD-1 signaling affects cristae morphology and leads to mitochondrial dysfunction in human CD8+ T lymphocytes. Journal for ImmunoTherapy of Cancer. DOI: 10.1186/s40425-019-0628-7

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