Molecularly imprinted polymer-based electrochemical sensor for L-tyrosine competition-mediated T cell exhaustion.

Nutrition competition exists in the tumor microenvironment (TME), which is considered as an important factor of T cell exhaustion. Various amino acids are the targets for both tumor cells and T cells, including L-Tyr, which plays an essential role in normal function of T cells. Herein, a novel sensing interface of MIP/Fc/PEDOT:PSS-PPy/graphite/Au established on a PCB substrate, was proposed for L-Tyr detection. This sensor was systematically characterized and showed excellent repeatability, stability, reproducibility, and specificity. Meanwhile, the sensor exhibited good detection capability, with a linear range of 1 nmol/L to 1 mmol/L, a limit of detection of 1.62 × 10-11 mol/L, and a sensitivity of 97.14 μA/(mol/L). An in-vitro co-culture model of T cells and tumor cells was established to mimic the TME, and its culture medium was used as real samples for L-Tyr determination via the proposed sensor. The results demonstrated that the failure of L-Tyr competition by T cells in the TME was a vital cause of their exhaustion, which was further validated by the IL-2 expression of T cells within the TME using ELISA. Collectively, our study is expected to provide a new strategy for tumor treatment, by supplementing exogenous amino acids to alleviate T cell exhaustion.