The work of Maxime Meylan, directed by Hervé Fridman and Catherine Sautès-Fridman in CARPEM team 8 (Inflammation, Complement and Cancer) has shown that the presence of B lymphocytes in tertiary lymphoid structures is associated with a good prognosis in renal cell carcinoma. This work, which constitutes a major advance in the field of immunotherapy, was published in the journal Immunity on February 28, 2022.
Tertiary lymphoid structures (TLS) are ectopic lymphoid structures that develop in non-lymphoid tissues such as tumors. They are aggregates of lymphoid cells organized in the form of lymph nodes, comprising a zone of T cells (killer cells) and a zone of B cells (antibody-producing cells). In their mature state, TLS are defined by the presence of a germinal center with T cells in close contact with B cells. Recent data suggest that the presence of mature SLTs and B cells in the tumor is associated with a good prognosis and predicts the therapeutic response to immune checkpoint inhibitors (ICIs) for many types of cancers. However, the molecular mechanisms by which these B cells influence the response to ICI treatments remain to be elucidated.
To address this question, the authors used the novel Visium 10X spatial transcriptomics technique that allowed both quantification and localization of B cell-specific gene expression. This study was conducted on several cohorts of renal cell carcinoma patients, and includes the HEGP ExhauCRF program initiated through work conducted in the CARPEM1 framework.
The results show that these cells are present in TLS at different stages of their maturation and in the form of cells differentiated into antibody-producing plasma cells, and more particularly IgG (immunoglobulin G). These antibodies are able to recognize and bind to tumor cells and induce their elimination. Interestingly, the presence of IgG bound to tumor cells is associated with a better response to immunotherapies and a better survival of patients, without disease progression. Thus, the presence of IgG-secreting plasma cells in TLS appears to be critical for the anti-tumor immune response.
Together, these results suggest that the detection of these IgGs within the tumor itself constitutes a new predictive marker of the response of patients to immunotherapy, and opens new innovative therapeutic perspectives in the development of personalized medicine.