T cell repertoire sequencing as a cancer's liquid biopsy—can we decode what the immune system is coding?

In oncology, liquid biopsy denotes the use of any biological fluid to detect cancer. Several approaches exist to perform such biopsy. These approaches target circulating tumor cells, circulating free DNA, exosomes, and more. The aim is to enable physicians to search for early signs of cancer with minimal patient burden. The effort to go after the minute amounts of cellular material through these technologies is remarkable, involving considerable financial investments and hundreds of research groups. Here, we highlight possible use of T cell repertoire sequencing for the same task. Repertoire sequencing has demonstrated a related capacity for early detection of cancer biomarkers via blood sampling, by focusing on the genomic sequences of T cell receptors found in the blood of potential patients. This mini-review aims to examine and assess the current methods of liquid biopsy and repertoire sequencing for their ability to uncover early signs of cancer, focusing on analytical validity as well as clinical utility.