T-cells from the liver and lymph nodes show promising potential for future treatments of liver cancer, according to a new study. Researchers at Karolinska Institutet have investigated how immune cells react to tumor-specific antigens in the complex environment surrounding liver cancer.
Liver cancer, or hepatocellular carcinoma (HCC), is a disease characterized by a unique and often immunosuppressive environment. This means that many patients do not respond to current immunotherapies. At the same time, T-cells, an important part of the body's immune defense, play a dual role in the tumor's development. On one hand, they can fight the tumor, but they can also contribute to an environment that protects the tumor from attack.
In a new study, published in the journal Gut, researchers at Karolinska Institutet analyzed T-cells from tumors, liver, and nearby lymph nodes in patients with advanced HCC. The study aimed to investigate whether it is possible to identify reactive T-cells despite the immunosuppressive environment.
Major advances
The researchers analyzed a total of 542 potential tumor-specific antigens, so-called neoantigens, from seven patients. Using advanced laboratory techniques, including single-cell RNA sequencing, they were able to show that certain T-cells reacted to these antigens.
"Our results show that T-cells collected from the liver and lymph nodes may have the potential to be used in new immunotherapies against liver cancer," says Anna Pasetto , research specialist at the Department of Laboratory Medicine at Karolinska Institutet.
The study showed that T-cells from liver fluid had profiles indicating both central memory function and cytotoxic properties - meaning an ability to fight tumor cells. T-cells from the lymph nodes, on the other hand, showed signs of exhaustion, meaning they had lost some of their function.
Opportunities for new treatments
An important finding is that the T-cells that reacted to the tumor's antigens carried specific receptors, which opens up the possibility of using them in new treatment methods, such as T-cell-based immunotherapy.
"By better understanding how these immune cells work and where they are located, we can take a step closer to more effective and personalized treatments for liver cancer," says Anna Pasetto.
The researchers now hope to use this knowledge to develop new immunotherapies that target tumor-specific antigens in liver cancer. The work also shows how important it is to analyze different parts of the tumor's microenvironment to get a complete picture of the disease.
This study gives hope that future treatments can harness the patient's own immune system to effectively fight liver cancer.
The study was conducted within the Karolinska ATMP Center and in collaboration with Neogap AB, University and University-Hospital of Modena and Reggio Emilia, Italy, Sahlgrenska Academy, University of Gothenburg, and Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas. The study has been funded by the Swedish Cancer Society, the Swedish Research Council, the Sjöberg Foundation, CIMED, Region Stockholm ALF funds.
Publication
" Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation ", Maravelia P, Yao H, Cai C, Nascimento Silva D, Fransson J, Nilsson OB, Lu YW, Micke P, Botling J, Gatto F, Rovesti G, Carlsten M, Sallberg M, Stål P, Jorns C, Buggert M, Pasetto A, Gut, online 27 januari 2025.
