Introduction

T regulatory (Treg) cells arise in the thymus when T cells exhibit an intermediate affinity for self-antigens presented via MHC II on thymic cells. In the periphery, tolerogenic dendritic cells (DCs) can also polarize T cells into Tregs if the T cells recognize self-antigens on these DCs. Because Tregs specifically respond to self-antigens, once they enter peripheral tissues or lymph nodes, they recognize antigen-presenting cells (APCs) displaying those self-antigens and foster a tolerogenic environment. This, in turn, inhibits the activation of any naïve T cells encountering the same APCs. Thus, Tregs play a crucial role in maintaining immune homeostasis by recognizing and regulating responses to self-antigens.

Meanwhile, identifying genuinely cancer-specific antigens is notoriously challenging. Tumor cells continually adapt to evade immune surveillance, often masking or minimizing expression of recognizable tumor antigens. However, once a cancer-specific antigen is identified, numerous immunotherapeutic interventions—such as monoclonal antibodies, CAR T cells, CAR NK cells, and oncolytic viruses—can be directed against it.

Here, I propose a novel angle: rather than focusing on pinpointing what sets cancer cells apart, we could theoretically exploit Tregs’ ability to recognize self-antigens on DC. By in vitro eliminating the recognized “normal” or “good” self-antigens, any remaining antigens would presumably be tumor-specific.