Revolutionizing Lung Cancer Treatment: Recent Breakthroughs in Immunotherapy

Lung cancer currently holds the leading cause of cancer-related deaths and ranks as the third most prevalent cancer across the world. Non-small-cell lung cancer (NSCLC), comprising squamous cell carcinoma (SCC), adenocarcinoma (ADC), and large-cell carcinoma (LCC), accounts for 80–85% of all cases, while small-cell lung cancer (SCLC), the most aggressive form, represents the remaining 15–20%. While targeted therapies have revolutionized the treatment landscape for lung cancer patients, they prove ineffective for individuals whose tumours do not possess the specific genetic alterations targeted by these therapies. In such cases, the integration of immunotherapy has emerged as a viable treatment approach, resulting in enhancements in both survival rates and overall quality of life. Recent advancements in immunotherapies have targeted T-cell inhibitory receptors, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), resulting in improved treatment outcomes for lung cancer. This review will provide an overview of the current state of immuno-oncology, focusing on factors influencing the effectiveness of immunotherapies. Despite the notable success achieved in certain cancer types, these targeted approaches still face limitations in most cases. Therefore, this review will also explore the challenges associated with resistance to current therapies, along with recent developments in basic tumour immunology. Moreover, it will discuss the triumphs and present difficulties in cancer immunotherapy. One of the significant hurdles in lung cancer lies in the development of cancer vaccines utilizing neoantigens supplied by the transporter associated with antigen processing (TAP) for tumours lacking mutant deficiency and displaying low levels of MHC-I/peptide complexes. To address these challenges, combining immune checkpoint inhibitors targeting PD-1 and CTLA-4 has proven beneficial, providing a controllable tolerance profile and therapeutic advantages against tumours. Additionally, the future of cancer immunotherapy could benefit from combining therapeutic vaccination targeting both mutant and non-mutant neoepitopes with immune checkpoint blockade (ICB) for improved specificity.