6.Conclusion
In recent years, therapeutic advances in cancer immunotherapy (CIT) have
emerged rapidly, reflecting the importance of human immune system
interactions with cancer, as well as the complex and highly regulated
nature of the immune system[70, 71]. Under the background of complex
immune network, point-to-point therapy has been unable to achieve
satisfactory tumor treatment effect, so combining various targeting axes
or immune checkpoints will become a new direction of tumor treatment.
Adenosine axis’s role in tumor microenvironment is mainly induced by
hypoxia, so some studies have also called it hypoxia-adenosine axis.
Extracellular adenosine increases in hypoxic conditions, and
simultaneously the expression of CD39 and CD73 improves
simultaneously[7]. Antihypoxia-adenosine therapy is synergistic with
other immune checkpoint inhibitors, such as CTLA-4 mAb and PD-1 mAb. The
combination of anti-hypoxia-adenosine strategies may enhance clinical
response to other immunotherapies and chemotherapy and
radiotherapy[67].With advances in the treatment of tumors with
immune checkpoint blockers such as CTLA-4 and PD-1/PDL1, more
therapeutic targets have been sought, including but not limited to the
immune targets in the adenosine energy axis mentioned above, in order to
overcome the problems of incomplete tumor regression or recurrence after
treatment[3].More identified immune checkpoint suppressor molecules
are emerging as new potential targets for tumor therapy. In the TME,
these molecular mechanisms may operate and may be supplementary to
immunotherapies that had been approved [22, 72, 73].When immune
escape of tumor cells becomes a difficult problem to conquer
tumors[74],the use of these immune checkpoint inhibitors can offset
immune escape of tumor cells to a certain extent and further improve the
response rate. Without increasing or even decreasing the adverse events
related to excessive damage of tissue, autoimmunity, and other
immune-associated side reactions associated with the use of immune
checkpoint inhibitors alone[18, 75-77].In the future, the treatment
trend of malignant tumors will be developed from point-to-point therapy
targeting individual immune checkpoints to the combination of immune
networks composed of various signaling pathways, such as adenosine axis.
Even therapies that are not traditionally considered immunotherapies can
induce or enhance antitumor immunity. As a result, they may force tumors
to upregulate immune checkpoints ,which can be blocked as part of a
combined strategy[76, 78-81].
7. Acknowledgments
This work was supported by the National Natural Science Foundation of
China Youth Project (grant no. 81900131), the National Natural Science
Foundation of China Youth Project (grant no. 8210010129), the Tianjin
Municipal Natural Science Foundation (grant no. 18JCQNJC80400), the
Tianjin Education Commission Research Project (grant no. 2018KJ043), the
Tianjin Education Commission Research Project (grant no. 2018KJ045), and
the Tianjin Science and Technology Planning Project (no.
20YFZCSY00060).Tianjin Municipal Health Commission Youth Project(grant
no. TJWJ2021QN001);Medjaden Academy & Research Foundation for Young
Scientists (Grant No. MJR20221011);Tianjin Key Medical
Discipline(Specialty) Construction project.