NK cells: key to success of DC-based cancer vaccines?

Abstract

The cytotoxic and regulatory antitumor functions of natural killer (NK) cells have become attractive targets for immunotherapy. Manipulation of specific NK cell functions and their reciprocal interactions with dendritic cells (DCs) might hold therapeutic promise. In this review, we focus on the engagement of NK cells in DC-based cancer vaccination strategies, providing a comprehensive overview of current in vivo experimental and clinical DC vaccination studies encompassing the monitoring of NK cells. From these studies, it is clear that NK cells play a key regulatory role in the generation of DC-induced antitumor immunity, favoring the concept that targeting both innate and adaptive immune mechanisms may synergistically promote clinical outcome. However, to date, DC vaccination trials are only infrequently accompanied by NK cell monitoring. Here, we discuss different strategies to improve DC vaccine preparations via exploitation of NK cells and provide a summary of relevant NK cell parameters for immune monitoring. We underscore that the design of DC-based cancer vaccines should include the evaluation of their NK cell stimulating potency both in the preclinical phase and in clinical trials.

Figure 1.

How NK cells can contribute to the antitumor efficacy of DC-based vaccination. Vaccine DCs can activate NK cells to (A) further stimulate vaccine and host DCs to advance sustained antitumor T-cell immunity, to (B) directly kill tumor cells, reducing the tumor burden and providing tumor cell material for further processing, and to (C) facilitate robust T-cell activation. Abbreviations: iDC, immature dendritic cell; mDC, mature dendritic cell; NK, natural killer cell; Th1, T helper 1; Treg, regulatory T cell.