28/02/2022
In a recent article published in Immunity, the team of Hervé Fridman and Catherine Sautès-Fridman shows that Tertiary Lymphoid Structures (TLS), when present in renal tumors, contain B lymphocytes that produce antibodies against tumor cells. This could explain the correlation between the presence of TLS, better response to immunotherapy and longer survival of patients.
Cancer immunotherapy involves stimulating a patient’s immune response to their cancer cells. This approach has revolutionized the treatment of many cancers, including kidney cancer. However, most patients are resistant to immunotherapy and it is important to understand the mechanisms of action of immunotherapy in order to treat them better.
Several years ago, the team of Hervé Fridman and Catherine Sautès-Fridman demonstrated the existence of tertiary lymphoid structures (TLS) within certain tumors: these are cellular clusters rich in immune cells, including B and T lymphocytes, a sort of micro-ganglion within the tumor. B cells are the cells that produce antibodies, while T cells are the killer cells of the immune system, which are usually non-functional in tumors, blocked in their function by molecules produced by the tumor cells.
The presence of TLS in a tumor is associated with a good response to immunotherapy.
To understand the role of SLTs in relation to immunotherapy, Maxime Meylan and his collaborators in the Inflammation, Complement and Cancer team at the Centre de Recherche des Cordeliers, analyzed a cohort of patients with kidney tumors.
In particular, they established by spatial transcriptomics a map of the localization of immune cells in these renal tumors, according to whether or not they contained SLT. They observed that in the presence of SLT, B lymphocytes are present at all stages of maturation, up to the antibody-producing plasma cell stage. And the presence of plasma cells is indeed correlated with the presence of antibodies that bind to and destroy certain tumor cells.
Furthermore, the presence of SLT in renal tumors was correlated with a better response to immunotherapy in the context of treatment with a T-cell “reactivator” and with longer survival of patients without disease progression.
These results suggest that the presence of antibodies secreted by plasma cells within tumors could potentiate the effect of T cell reactivator treatment, in particular via the release of antigens by the destroyed tumor cells. They make it possible to identify patients likely to respond to immunotherapy by analyzing their tumors, and to study new therapeutic avenues via the cooperation of B and T lymphocytes within tumors.
Article reference:
Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer, Maxime Meylan, et al. Immunity, 28 February 2022.