The immune system helps protect us against cancer, however immune cells often become dysfunctional within the tumor environment, which leads to disease progression. Elucidating the mechanisms by which immune cells lose their functional capacity in tumors is critical to developing next-generation immunotherapies. The Geiger laboratory at the IRB used mass spectrometry-based proteomics to profile immune cells isolated from tumors of patients with liver cancer, which led to the identification of new potential targets for immunotherapy.
Bellinzona, May 30, 2023 – To study the phenotypes of immune cells in tumors of hepatocellular carcinoma (HCC) patients, researchers from the IRB isolated different immune cell types including T cells, NK cells, monocytes and macrophages from tumors, liver and blood and analyzed their proteomes using mass spectrometry-based proteomics. This resulted in an extensive dataset on immune cell proteomes that is accessible through www.immunomics.ch/hcc.
“Our results identified AFAP1L2 and SGPL1 as new potential therapeutic targets to improve immune responses to cancer” says Fernando Canale, a former postdoctoral fellow at IRB and first author of the study. A key takeaway is that AFAP1L2 interferes with the effector function of chronically stimulated T cells. Importantly, its ablation in T cells enhances anti-tumor activity in pre-clinical models.
Another finding was that tumor macrophages upregulate SGPL1, an enzyme that degrades sphingosine-1-phosphate. Ablation of Sgpl1 in murine macrophages increases their inflammatory phenotype and anti-tumor activity.
The study, recently published in the journal Cell Genomics, was conducted by researchers from the IRB (Bellinzona, Switzerland), affiliated to the Università della Svizzera italiana (USI), in collaboration with colleagues from the Universities of Bologna (Italy), Mannheim (DE), Dresden (DE), Basel (CH), Bern (CH), and the Ente Ospedaliero Cantonalein Ticino (CH).