FIBROCAN · Defining the immunological interplay between fibroblastic reticular cells and anti-tumour T cells

Defining the immunological interplay between fibroblastic reticular cells and anti-tumour T cells

Our project was designed to answer the question of why and how particular cells called fibroblastic reticular cells (FRCs) found in lymph nodes allow metastasis to happen. The FRCs are the most frequent stromal cell (non-white blood cell) in the lymph node and recent work shows they heavily regulate immune cell activity and survival. We predicted that this regulation is exactly why tumour cells reaching lymph nodes escape detection and deletion. An important part of this detection and deletion process are the T cells that are present in the lymph nodes. T cells are specialized Immune cells that patrol their environment constantly and delete cells that are harmful such as cancer cells. The persistent dogma has been that lymph nodes are a hostile environment for tumour cells. However, a variety of cancers preferentially metastasise to the lymph nodes that are close in proximity to the origin of the tumours. Research is slowly overturning the initial dogma by showing that lymph nodes are a site where T cell responses are censored. The reason for this is probably that the lymph node site can be rich in stimulants that would otherwise continuously activate the T cells and lead to chronic inflammation. At the commencement of the project, the state of the art was that mouse FRCs prevent T cell activation in the lymph node by secreting signals that dampen the T cell response. Our research sought to test this observation in human systems and pose the following question in relation to tumour metastasis: if the escape mechanism of tumour cells is related to these FRCs, how does it occur, and can we identify new targets for therapies that would reverse the inhibitory effect that they place on T cells, to allow early deletion of metastatic tumour cells. This would be important to the wider community as it would open up a new range of therapies that target metastasis specifically and even perhaps allow preventative treatment in high risk patients. Our overall objectives were to SO1: To chart the fate of anti-tumour T cells following suppression by FRCs. SO2: To identify tumour immunotherapy targets presented by tumour cells but not FRCs. SO3: To test therapeutic fibroblast populations for censorship of anti-tumour T cells.

Data: CORDIS, © European Union