Immune checkpoint blockers (ICB) have emerged as a promising new class of antitumor agents which significantly change the treatment landscape in a range of tumors; however, cancer patients benefited from ICB-based immunotherapy remains limited, scoring the need to explore the combination treatments with synergistic mechanisms of action. Axl receptor tyrosine kinase critically involves in the carcinogenesis of multiple cancers due to its dual roles in both promoting cancer invasion and metastasis and suppressing myeloid cell activation and function. Here, we found that Axl inhibition by tyrosine kinase inhibitors induces antitumor efficacy critically depending on immune effector mechanisms in two highly clinical relevant murine tumor models. Mechanistic investigation defined that Axl inhibition reprograms the immunological microenvironment leading to the increased proliferation, activation and effector function of tumor-infiltrating CD4+ and CD8+ T cells possibly through preferential accumulation and activation of CD103+ cross-presenting dendritic cells. More importantly, we show that Axl inhibition induces an adaptive immune resistance evidenced by unregulated PD-L1 expression on tumor cells and combined Axl inhibition with PD-1 blockade mounts a potent synergistic antitumor efficacy leading to tumor eradication. Thus, Axl-directed therapy in Axl expressing tumors could hold a great potential to subvert the innate and/or adaptive resistance to and broaden the coverage of population benefited from ICB-based immunotherapy.

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A stable dihydroxybenzene sensor was fabricated by electrochemical deposition of Zn/Al layered double hydroxide film on glassy carbon electrode (LDHf/GCE). The sensitive and facile electrochemical method for the simultaneous determination of catechol (CA) and hydroquinone (HQ) under coexistence of resorcinol (RE) has been achieved at the LDHf/GCE in phosphate buffer solution (pH 6.5). Under the optimized conditions, the differential pulse voltammetry response of the modified electrode to CA (or HQ) shows a linear concentration range of 0.6 mM to 6.0 mM (or 3.2 mM to 2.4 mM) with a correlation coefficient of 0.9987 (or 0.9992) and the calculated limit of detection is 0.1 mM (or 1.0 mM) at a signal-to-noise ratio of 3. In the presence of 50 mM isomer, the linear concentration ranges for CA and HQ are 3.0 mM to 1.5 mM and 12.0 mM to 0.8 mM, respectively. The detection limits are 1.2 mM and 9.0 mM. Further, the proposed method has been performed to successfully detect dihydroxybenzene isomers in analysis of real samples, such as water and tea.