Harnessing unconventional T cells to understand tumor immunity and improve immunotherapy in colorectal cancer

Unconventional T cells, in particular mucosal-associated invariant T (MAIT) cells and gd T cells, have potent effector functions that may be relevant for tumor immunity.

However, their contribution to anti-tumor immunity is still unclear, and the potential to use unconventional T cells for immunotherapy needs to be determined.

In this 4-year project, we will test the hypothesis that unconventional T cells critically contribute to anti-tumor immunity in colorectal cancer (CRC) and investigate if they are suitable candidates for immunotherapy.

We will use fresh tissue from CRC patients to perform a detailed and unbiased assessment of subpopulations of unconventional T cells in the tumor microenvironment, both in primary tumors and in metastases.

We will evaluate clonality, phenotype, and pro- and anti-tumorigenic effector functions, as well as the impact of the tumor microenvironment in different settings.

We will also explore the molecular mechanisms of unconventional T cell cytotoxicity, and if they have the capacity to kill primary tumor cells. Additionally, we aim to develop methods to improve unconventional T cell cytotoxicity and migration to tumor tissues.

These studies will generate an exhaustive understanding of tumor-infiltrating unconventional T cells and their contribution to tumor immunity.

They will also advice development of improved immunotherapy for CRC patients based on unconventional T cell activation and adoptive transfer.