Understanding the role of ILC3 in TLS formation – ILC3formTLS

The immune system plays a central role in the response to anticancer treatment. T CD8 lymphocytes and Natural Killer (NK) cells can, using their cytotoxic ability, directly kill tumor cells but numerous immunosuppressive mechanisms aim at limiting those antitumor responses. Immune checkpoint inhibitors (ICI) remobilize cytotoxic cells against the tumor and ICI are considered a significant improvement in anticancer treatment. The efficacy of ICI was recently positively correlated with the presence of tertiary lymphoid structures (TLS) within tumors.
TLS are ectopic lymphoid structures that appear in inflamed non-lymphoid tissues, mainly composed of T and B lymphocytes, and are of good prognosis in many solid cancers. However, events leading to the development of TLS are not fully understood, and literature suggests that its share some similarities with the events happening during the development of secondary lymphoid organs (SLO) such as lymph nodes, where Lymphoid tissue inducer (LTI) cells are essential. If LTI can only be found during fetal life, CCR6+ expressing group 3 innate lymphoid cells are often called LTI-like ILC3 as they are phenotypically and functionally close. It is therefore believed that ILC3 could participate in the development of TLS, much like LTI with the SLO.
We observed that CCR6+ ILC3 are responsible for a massive rise in immune cells infiltrating the tumor after a cisplatin treatment. We also observed the development of lymphoid aggregates in the tumor after cisplatin, only in the presence of ILC3, suggesting a possible spatial organization of the immune infiltrate triggered by cisplatin and driven by ILC3. These data allow me to think that CCR6+ ILC3 actively participate in the formation of TLS and allow a better antitumor immune response from within the tumor. In this project, I will decipher the link between ILC3 and TLS formation and I will develop strategies to improve TLS generation in tumor to fight against CKI therapy resistance.