Immunotherapy

Abstract

The prognosis of advanced small cell lung cancer and non-small cell lung cancer was improved with development of chemotherapy and molecular target therapy but still remains poor. Recently, immunotherapy, especially immune checkpoint inhibitor that blocks negative co-stimulator of immune activation, showed promising efficacy. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a negative co-stimulator expressed in T cell. Interaction signal with CD80/86 and CTLA-4 between antigen-presenting cell and T cell leads to T-cell suppression. In malignant melanoma, ipilimumab, anti-CTLA-4 antibody, improved survival. On the other hand, programmed death-1 (PD-1) and its ligand PD-L1 are also negative co-stimulators between T cell and tumor cell. And anti-PD-1 antibody impedes the interaction with PD-1 and PD-L1 between T cell and tumor cell and leads to avoid apoptosis of T cell. Anti-PD-1 therapy showed survival benefit in malignant melanoma and non-small cell lung cancer in phase III study. However, it is unclear who can get the benefit. Expression of PD-L1 in tumor cell is expected as a predictive biomarker in non-small cell lung cancer. However, there remain many problems to estimate PD-L1 expression such as adequate antibody, cutoff value, and sample quality. Mutation burden in tumor cell is another promising predictive factor in immune checkpoint inhibitor. However, we need to investigate more validated marker. Further study to investigate the predictive factors and combination with other modalities or immunotherapies was warranted.