Lung cancer poses a global threat to human health, while common
cancer treatments (
chemotherapy and targeted
therapies) have limited efficacy.
Immunotherapy offers hope of sustained remission for many patients with
lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the
adenosine (
ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell
lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of
ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the
ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the
ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in
lung cancer. As such, a timely review of the potential value of the
ADO pathway in combination with
immunotherapy strategies for
lung cancer is warranted. This comprehensive review first describes the role of
ADO in the formation of a lung
tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of
ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of
ADO inhibitors combined with
immune checkpoint blockers to improve the
lung cancer immunosuppressive microenvironment.