The PD1/PDL1 pathway plays an important role in the immune paralysis of the body caused by non-small cell lung cancer (NSCLC). Blocking immune paralysis with PD1/PDL1 inhibitors has been shown to have a significant effect on the treatment of progressive NSCLC and may be better than the current standard of care. Non-small cell lung cancer has been thought to be unable to elicit an immune response, i.e., immune cells are unable to attack this type of lung cancer cell. Early studies of relatively non-specific immunotherapy failed to demonstrate effectiveness in lung cancer. The Society of Thoracic Oncology remains skeptical of immunomodification therapy. However, the results of clinical studies in recent years have revived interest in new immunotherapies for lung cancer. Of particular interest are two approaches, namely lung cancer vaccines and immune test site inhibition. The former enhances the exposure of tumor antigens to the body and initiates the activity of cellular immunity, while the latter aims to suppress the immune paralysis of the body and further enhance the immune attack of immune cells against tumor cells. Two immune test sites have been identified, namely cytotoxic T cell-associated antigen 4 (CTLA-4), expressed on the surface of activated T cells, and programmed death receptor 1 (PD1).CTLA-4 functions mainly in lymph nodes to regulate early T cell activation by interfering with antigen-specific T cell activation induced by dendritic cells (DCs). After phagocytosis of tumor antigens, dendritic cells (DCs) process the antigens and, together with their own histocompatibility complexes (MHC), deliver them to T cells. At the same time, dendritic cells (DCs) are stimulated to express a molecule called B7 on their surface. This process occurs in the lymph node when the T cell receptor recognizes the tumor antigen on the MHC and CD28 on the T cell surface binds to B7 on the surface of the dendritic cells (DCs). The activation of T cells is completed when both signals are present. These activated T cells, which recognize the antigen, can then travel to the site of the tumor. After recognizing the tumor antigen again at the tumor site, these T cells can proliferate and secrete cytokines to further rally other immune cells to attack the tumor cells. CTLA-4 is an immune test point molecule that normally reduces autoimmune responses and excessive inflammatory responses. In tumor CTLA-4 interferes with T cell activation and T cell attack against tumor. cTLA-4 also binds to B7 while competitively interfering with CD28 binding of T cells to B7. Moreover, the binding of CTLA-4 to B7 is stronger than that of CD28 to B7, thus interfering with the second signal of T-cell activation, and as a result, T-cell activation is inhibited. The newly developed anti-CTLA-4 monoclonal antibody, Ipilimumab, interferes with the inhibitory effect of CTLA-4 and restores T-cell activity. Programmed death receptor 1 (PD1) with its ligand (PDL1) is another immune test point pathway. Some tumor cells express PDL1, which results in immune paralysis. Inflammation in the tumor microenvironment is able to induce PDL1 expression by tumor cells. tumor cell-expressed PDL1, when combined with activated T cells, can deliver inhibitory signals and cause immune paralysis. Monoclonal antibodies against PD1 and PDL1 block PDL1 signaling, allowing T cells to proceed to attack tumor cells. After recognition of tumor antigens by T cells, dendritic cells (DCs) express B7.1 and B7.2 , which bind to CD28 on T cells and deliver a second signal to initiate T cell activation (Figure 1.B). However, CTLA-4 binds more strongly to B7.1 and B7.2 than CD28. The anti-CTLA-4 monoclonal antibody Ipilimumab inhibits CTLA-4 binding to B7.1 and B7.2, allowing T cells to better exert their anti-tumor effects. This monoclonal antibody has shown clinical antitumor effects in melanoma, kidney and lung cancer and is now FDA approved for the treatment of melanoma. Unlike CTLA-4, PD1 acts during peripheral tissue inflammation to limit the autoimmune response. Lung cancer and several other tumors express the PD1 ligand (PDL1). After PDL1 binding to activated T cells in the tumor microenvironment, PD1 is able to deactivate antigen-specific T cells from attacking tumor cells. Several monoclonal antibodies against PD1 and PDL1 are now being clinically studied for their anti-lung cancer effects. Two studies have been published in the prestigious New England Journal of Medicine. One study evaluated an anti-PD1 monoclonal antibody (BMS-936558), and the other study evaluated an anti-PDL1 monoclonal antibody (BMS-936558). The half-life of the anti-PD1 monoclonal antibody BMS-936558 in the blood is 12-20 days. It is administered clinically every 2 or 3 weeks.122 In chemotherapy-naïve progressive lung cancer, BMS-936558 was administered intravenously every two weeks for two years. the survival rate without cancer progression after 24 weeks was 33%. There were several patients with squamous cell lung cancer and non-squamous cell lung cancer histologic types in NSCLC who had sustained results with BMS-936558. BMS-936558 is currently in two Phase III clinical studies evaluating the therapeutic effects of progressive NSCLC. The studies also include combination chemotherapy and targeted therapy. Further studies are to clarify the mechanism of sensitivity and resistance to PD1/PDL1 blockade and the markers that predict response and survival to these treatments.