Breast cancer: identification of the players involved in the tumor invasion in the lymph nodes
The lymphatic system is a vital component of the immune system. The lymph modes, the center of the lymph collection system, contain many types of immune cells responsible for eliminating pathogens, damaged cells and also cancerous cells.
Unfortunately, sometimes the immune cells present in the lymph nodes are not able to destroy the tumor. Then, the tumor cells can also spread elsewhere in the body. In breast cancer, the underarm lymph nodes are the first to be affected. The discovery that they have been invaded is a factor in choosing subsequent treatment. But what happens in these organs when the tumor invades them? Why can’t the immune system get rid of it? Would it be possible to try to slow down the spread of the cancer?
To answer these questions, Eliane Piaggio, head of the “Translational Immunotherapy” team in the “Immunity and Cancer” Inserm unit at Institut Curie, and her colleagues, studied invaded and non-invaded lymph nodes as well as tumors taken from patients with breast cancer. In Nature Communication, they describe, for the first time, the role of the regulatory T cells (Tregs) in the lymph nodes.
“This sub-population of T cells is vital for the homeostatis of the immune system. It controls and regulates the immune reactions to maintain self-tolerance. Thus, it prevents runaway of the other immune cells. But in the case of cancer, we found that it reduced tumor immunity, and encouraged the spread of the cancer,” explains Eliane Piaggio. It has been shown in the past that tumors cheats/fools the immune system, and in particular the Tregs: their activity becomes excessive and prevents the white blood cells from destroying the cancer cells.
A pro-tumor action of these lymphocytes is also exerted in the lymph nodes, as shown by the work of Eliane Piaggio’s team. “As soon as the tumor metastasizes in the lymph nodes, there is an increase in the regulatory T cells. We have even discovered that the cells present in the tumor and those found in the lymph nodes come from the same clones, which means that they share the same information. Moreover, these Tregs, all express unique molecules” Eliane Piaggio continues.
Indeed, by analyzing the transcriptome of the tumor and lymph node Tregs, researchers identified a unique molecule: the CD80 marker. This protein could become an interesting therapeutic target and pave the way for the development of a new immunotherapy. The aim would then be to eliminate the regulatory lymphocytes to unlock the immune system’s action against the tumor. “Targeting these cells could be a solution for many tumors. But every tumor is different, and the same is true for Tregs. We therefore have to identify the unique molecular targets each time and develop antibodies specifically directed against them. This is precision medicine”, explains Piaggio, who is currently carrying out similar work in lung cancer patients.
Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients. Nicolas Gonzalo Núñez, Jimena Tosello Boari, Rodrigo Nalio Ramos, Wilfrid Richer, Nicolas Cagnard, Cyrill Dimitri Anderfuhren, Leticia Laura Niborski, Jeremy Bigot, Didier Meseure, Philippe De La Rochere, Maud Milder, Sophie Viel, Delphine Loirat, Louis Pérol, Anne Vincent-Salomon, Xavier Sastre-Garau, Becher Burkhard, Christine Sedlik, Olivier Lantz, Sebastian Amigorena & Eliane Piaggio. Nature Communications volume 11, Article number: 3272 (2020)