Unconventional T cells in tumor immunity

Unconventional T cells have a conserved T cell receptor and respond instantly to stimulation by cytotoxicity and cytokine production, and may thus be crucial for antitumor immunity. However, the knowledge about unconventional T cells is still scarce, especially in cancer settings.

The novel checkpoint blockade therapy has improved tumor immunotherapy considerably, but many tumor types, among them colorectal cancer (CRC), still respond poorly and new treatment options are urgently needed.

The aim of this proposal is to evaluate the contribution of unconventional T cells to tumor immunity, and determine if their effector functions can be improved by immunotherapy.

We will use tissue material from CRC and lung cancer patients to perform a detailed and unbiased evaluation of subpopulations of mucosal-associated invariant T (MAIT), gd T, and invariant NKT (iNKT) cells in the tumor microenvironment.

In particular, production of anti- or pro-tumorigenic cytokines and cytotoxic potential will be determined in different settings.

Studies will also be performed to investigate how the tumor microenvironment affects unconventional T cell function and the effect of checkpoint blockade on unconventional T cells.

The possibility to use unconventional T cells for immunotherapy, either by directly administering expanded cells or by modulating the function of endogenous, tumor-infiltrating cells has not yet been properly evaluated, but is likely to open new avenues for cancer treatment.