New method is better able to map immune response and paves way for new treatments

Immune cells such as T and B cells are central to the body’s defence against both infections and tumours. Both types of immune cells express unique receptors that specifically recognise different parts of unwanted and foreign elements, such as bacteria, viruses and tumours. Each immune cell and its progeny has its own specific receptors, and in each human body there are billions of different immune cells with unique receptors.

Researchers at Karolinska Institutet, KTH Royal Institute of Technology and SciLifeLab have now developed a method that is able to both identify the different B and T cell receptors and reveal their location in human tissue.

Many areas of application

“Since activated immune cells are often found close to the targets that they attack, we want to be able to map the cells that are indeed closest to a tumour or infection,” says Camilla Engblom, assistant professor at the Department of Medicine (Solna), Karolinska Institutet and one of the study’s three lead authors along with Kim Thrane, KTH/SciLifeLab, and Qirong Lin, Karolinska Institutet. “It hasn’t been possible to identify both B och T cell receptors in their microenvironments using previous methods.”

According to Dr Engblom, there is a wide range of areas in which the new technique can be put to clinical use in the future.

“In cancer, the method can identify T cells that potentially attack the tumour,” she says. “They could then be used as cell therapy against cancer. We can also identify unique receptors on the B cells that are released as antibodies in specific areas of the tumour. These antibodies can be produced in the lab with relative ease and eventually give rise to novel therapies. Another field is autoimmune diseases, where the immune system attacks healthy tissue. The new technique could be used to identify the immune cells that do this and increase the chances of finding exactly what it is they attack.”

An important step forward

Jeff Mold, one of the principal investigators of the study and researcher at the Department of Cell and Molecular Biology at Karolinska Institutet, sees the new method as an important step forward.

“Identifying these unique immune receptors is like trying to find a needle in a haystack, especially when it comes to autoimmune diseases,” he says. “With most current methods, you destroy the tissue, which means not only that you get different immune cells mixed up, but also that some cells die in the process. With this method, we preserve the cells where they are and we can see cells that would otherwise have been lost.”

Dr Mold believes that the ability to identify B cells is arguably the main benefit of this new method.

“T cells have been a popular research target, while the B cells have been a little overlooked, especially in cancer,” he says. “But now we can track how B cells develop and expand direct in tissue.”

The study was financed by the Swedish Research Council, the Swedish Cancer Society and the EU research and innovation programme Horizon 2020.

Potential conflicts of interest: Camilla Engblom, Kim Thrane, Jeff Mold, Jonas Frisén, Joakim Lundeberg and Qirong Lin are inventors of a patent that covers this work. Camilla Engblom, Kim Thrane, Qirong Lin, Alma Andersson, Hosein Toosi, Sami Saarenpää, Jeff Mold, Joakim Lundeberg and Jonas Frisén are scientific consultants for 10x Genomics, which holds intellectual property rights to this technology. Jeff Mold holds shares in Pacific Biosciences.

Facts: Spatial transcriptomics of immune cells

The method of spatial transcriptomics was developed in 2016 by professors Jonas Frisén at Karolinska Institutet and Joakim Lundeberg at KTH Royal Institute of Technology, who are co-authors of this study. It was named “Method of the Year 2020” by the journal Nature Methods. The new method is an upgrade of the original method that now makes it possible for researchers to map the immune cells’ receptors and their exact location in tissue, which was previously not possible to do for B and T cells at the same time. Source: Camilla Engblom and Jeff Mold.

Publication: “Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics”, Camilla Engblom, Kim Thrane, Qirong Lin, Alma Andersson, Hosein Toosi, Xinsong Chen, Embla Steiner, Chang Lu, Giulia Mantovani, Michael Hagemann-Jensen, Sami Saarenpää, Mattias Jangard, Julio Saez-Rodriguez, Jakob Michaëlsson, Johan Hartman, Jens Lagergren, Jeff Mold, Joakim Lundeberg, Jonas Frisén. Science, online 7 December 2023, doi: 10.1126/science.adf8486.