Recently immunomodulatory strategies, particularly the blockade of the PD-1/PD-L1 axis to rejuvenate lymphocyte inhibition, have revolutionized the field of oncology. Upon chronic tumor-driven antigen stimulation, programmed death-1 (PD-1) is expressed on lymphocytes and binds to its respective ligand - PD-L1 - on the cancer cells.
Subsequently, lymphocyte exhaustion - an unresponsive and nonfunctional state – is induced, mainly in cytotoxic T lymphocytes (CD8+), mediators of tumor cells killing. In consequence, the malignant growth escapes rejection. Blockade by interfering antibodies reinvigorates a patient’s endogenous anti-tumor immunity.
Despite recent successes, many questions remain unanswered.
Still, the majority of patients does not benefit from this treatment and even more important, a predictive marker indicating tumor response does not exist until today. Here, I aim to develop assays using patient blood and tumor tissues to predict a functional adaptive immune response towards the tumor based on the transcriptional state of T cell functionality.