Guiding the „misguided“ – functional conditioning of dendritic cells for the DC-based immunotherapy against tumours
ABSTRACT
The concept of DC-based tumour vaccine has been tested both clinically and experimentally for the past two decades. Even though only limited success has been achieved to date, DC vaccination remains a promising immunological approach against tumours and deserves further exploration. It aims to elicit and establish specific immunity to destroy tumours. By such an approach, DC are used not only as a vector to deliver tumour antigens, but also as a „natural adjuvant“ to boost vaccine efficacy. Tumours are however of mutated „self“, to which the host immune system is essentially tolerated in the absence of external perturbation otherwise. Such a live cell-based approach is unfortunately extremely sensitive to, hence its efficacy inevitably limited by, the tumour microenvironment. Certain immunosuppressive mechanisms triggered by the tumour cells are therefore major obstacles against successful DC vaccination. Attempts have since been made in order to overcome these hurdles. This brief review summarises some of the earlier and current findings, and compares the effectiveness of various approaches used in these studies. It focuses particularly on strategies aimed at enhancing DC immunogenicity, through molecular modifications and functional conditioning of the cell vectors, targeting both the positive and negative regulators of DC functions. By dissecting the roles of DC in immunity versus tolerance induction, and the very mechanisms underlying autoimmunity, we examine further and try to explain how the suppressed or „misguided“ immunity may be alternatively switched-on and more effectively redirected for cancer therapy.