The CD73-adenosine axis in NSCLC: expression regulation, pro-tumor mechanisms, and combination therapy

In non-small cell lung cancer (NSCLC), the CD73-adenosine pathway plays a key role in immune metabolic regulation. In clinical trials, therapies targeting the CD73 pathway have shown significant promise. This review summarizes the expression regulation and multidimensional pro-tumor mechanisms of the CD73-adenosine axis and the latest developments in therapies targeting CD73 in NSCLC. The review first characterizes CD73 expression in NSCLC, with particular emphasis on its distribution across malignant, immune, and stromal cell populations within the tumor microenvironment. The regulatory network governing CD73 expression is then summarized, followed by a discussion of the adenosine-dependent and adenosine-independent mechanisms through which CD73 promotes tumor progression. The biological rationale for combining CD73-targeted therapies with standard treatment regimens is also discussed. Finally, recent clinical advances in CD73-targeted therapies are reviewed, together with future research directions, including the development of dynamic biomarkers and the exploration of novel combination strategies to facilitate precision immunotherapy in NSCLC.