**9. Conclusions**

ICIs have transformed the treatment of lung cancer. Although the number of patients with long-term survival after ICI treatment is significantly greater than that with previous therapies, such cases are limited, and novel therapies such as methods of selection and combination therapies that enhance efficacy remain an important issue to be resolved. The development of predictive factors for immunotherapy is crucial with regard to the efficacy of future treatment gains. Although both PD-L1 and TMBs may be helpful in case selection, it is now clear that resistance can develop by more than one mechanism. In future, further optimized treatments can be expected by combining cancer genomic information with the assessment results of cellular components from the tumor microenvironment. Although immunochemotherapy has shown great success in the treatment of lung cancer, it is expected that treatment will be individualized further on a case-by-case basis in future and will be improved by the development of combination treatments with targeted or cellular therapies, or new combinations of immunotherapies. Future challenges will likely involve targeting the correct immunotherapy to the correct immune microenvironment at an appropriate time. On the contrary, although not detailed in this article, the side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecularly targeted drugs, spanning various organs including the skin and the digestive, respiratory, thyroid, and pituitary glands. These are considered side effects due to excessive autoimmune reactions, which are relatively infrequent and if present, are usually mild, allowing continued treatment with immune checkpoint inhibitors under careful management. However, adverse event management during treatment requires caution, as moderate to high immune-related adverse events are associated with markedly reduced organ function and quality of life, and fatal consequences have also been reported. Establishment of more appropriate usage methods such as the development of biomarkers and of combined immunotherapy is highly desired in the future.

**Author Contributions:** Writing—original draft preparation, K.O., Y.C., J.U.; writing—review and editing, J.U., T.S., Y.M., M.I., Y.K. and T.Y.; supervision, K.T. All authors have read and agreed to the published version of the manuscript.

**Acknowledgments:** We would like to thank Editage (www.editage.jp) for English language editing.

**Conflicts of Interest:** The authors declare no conflicts of interest.
