Tumor Immune Microenvironment and Immunotherapy in Non-Small Cell Lung Cancer: Update and New Challenges

Non-small cell lung cancer (NSCLC) is a serious threat to the health of older adults. Despite the significant progress in immunotherapy, effective treatments for NSCLC remain limited. The development of tumors indicates failure in immune surveillance and the successful immune escape of tumor cells. Research on the tumor immune microenvironment (TIME) revealed these opposing immune processes and contributed to the discovery of new methods to suppress the immune escape and restore the immune surveillance functions. This paper aimed to provide updates on the current findings regarding the relevance of TIME in NSCLC treatment. It also aimed to introduce the TIME, immune editing, cancer immunotherapy, and new challenges. Based on the clinical data, the combination of neoadjuvant chemotherapy and immune checkpoint inhibitor (ICI) therapy is suitable for patients with NSCLC who are not eligible to undergo surgery. Combined ICI therapy after epidermal growth factor receptor (EGFR)/tyrosine kinase inhibitor (TKI) therapy should be considered in patients with EGFR mutations. Chemoradiotherapy may increase the density of CD8⁺ lymphocytes, which is significantly associated with better prognosis. For older patients and those with advanced-stage disease, regional tumor treatments, such as stereotactic radiation therapy and percutaneous cryoablation, may be more suitable, but further studies are needed to confirm this. In conclusion, restoring immune surveillance is as important as removing cancerous tissues; further studies that include the use of combined treatment methods, individualized treatment plans, and immunonutrition are warranted.