Innate-like T (ILT) cells, such as iNKT, MAIT and Vγ9Vδ2 T cells, have been exploited both as effectors and as adjuvants in cancer immunotherapy studies, including in a clinical trial at our own centre. Advanced malignancies are often associated with immune suppression, so knowledge of the function of ILTs in patients with cancer, and the impact of immune-modulatory treatments such as checkpoint blockade, is important to inform the design of future ILT cell-activating immunotherapies.

To address this, we are conducting three complementary studies: 1. a cross-sectional study to assess the frequency and function of ILTs in men with localised and advanced prostate cancer, compared to age-matched male controls; 2. in vitro investigations using healthy human blood cells to assess the expression and function of immune checkpoints on ILTs, and their amenability to blockade by clinically-available inhibitors; and 3. a longitudinal study examining ILT frequency and function before and during PD1 blockade for metastatic melanoma.

To date, we have recruited 36 men with prostate cancer (both low grade, indolent disease and metastatic, castrate-resistant disease), 20 healthy male age-matched controls and 10 patients receiving pembrolizumab for melanoma. We have developed a suite of assays to characterise ILT frequency and function from peripheral blood mononuclear cells, preliminary results of which indicate a functional impairment of blood iNKT cells from men with prostate cancer. Finally, our in vitro assays indicate that iNKT and MAIT cells express PD1, and that PD1 ligation inhibits their function.

We expect these studies to contribute to the development of ILT cell-targeted immunotherapies in patients with cancer, in terms of patient selection and to inform the rational design of combination trials with checkpoint blockade.