T cell immunity in intestinal tumors

Immune responses influence patient outcome in most cancer types, and the most important cell types for anti-tumor immunity are cytotoxic and cytokine producing lymphocytes. These lymphocytes include conventional CD8+ cytotoxic T cells, NK cells, and Th1 cells, and also unconventional T cells like mucosa-associated invariant T (MAIT) cells and γ/δ T cells.

Regulatory T cells (Treg), on the other hand, can inhibit the function of cells with anti-tumor activity and thereby help the tumor to escape immune recognition. Furthermore, lymphocytes need to leave the circulation and enter into the tumor itself in order to execute tumor-promoting or repressing responses.

The aim of our project is to elucidate the role of different T cell populations in colorectal cancer (CRC), both primary tumors and peritoneal metastases, and understand how they influence local anti-tumor immunity and lymphocyte recruitment to tumors. These studies are particularly important as several immunomodulatory therapies aimed at promoting anti-tumor T cell immunity by reducing Treg activity are currently being implemented, so-called checkpoint blockade therapy.

In order to perform these studies, we use tissue resection material from cancer patients and blood from volunteers. More specifically, we are studying i) the expression of endothelial adhesion molecules and chemokines in unaffected and tumor tissues, and how these shape the repertoire of tumor-infiltrating lymphocytes, ii) the activity of unconventional T cells in primary and metatstatic CRC, iii) cytotoxic mechanisms in tumor-infiltrating T cells, iv) the ability of regulatory T cells to influence lymphocyte recruitment and T cell effector functions in the tumor microenvironment. In addition, we also examine the composition of immune cells infiltrating peritoneal metastases and their production of cytokines and cytotoxic mediators. We also perform long-term follow up of patient outcome related to the immunological parameters that we characterize. The knowledge gained from these studies will be used to improve current strategies for immunotherapy against gastrointestinal tumors.