New advances on the interaction between internal and external factors in the tumor microenvironment of solid tumors

The tumor microenvironment is a dynamic and balanced internal environment that accompanies the whole process of tumor development, invasion, and metastasis. Immune checkpoint therapy, chimeric antigen receptor cell therapy, oncolytic virus therapy, and bispecific antibody therapy are the most anticipated immunotherapy methods. These therapies break the microenvironment conducive to tumor growth by regulating anti-tumor immunity. The underlying characteristics of the tumor immune microenvironment are the key scientific issues to break the bottleneck of solid tumor immunotherapy. With the rapid development and application of single-cell sequencing technology and spatial oncology technology, scientists have gradually recognized more complex details of cell-cell interaction in the tumor microenvironment.

We review the latest research progress in tumor immune escape, tumor metabolic reprogramming, and neuroimmunity [PubMed database published between 2000 and 21 May 2025]. We analyze the effects of these biological processes on anti-tumor immunity, to seek breakthroughs for the design of combined immune therapy. We also summarize the latest research on major immunotherapies mentioned above.

Through the integration of frontier and hot basic scientific issues and the design of clinical trials, we hope to identify the potential combination treatment plan for immunotherapy to overcome the tumor microenvironment of solid tumors.