Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review

Abstract

The treatment of lung cancer has changed drastically in recent years owing to the advent of immune checkpoint inhibitors (ICIs). A 1992 study reported that programmed cell death-1 (PD-1), an immune checkpoint molecule, is upregulated during the induction of T cell death. Since then, various immunoregulatory mechanisms involving PD-1 have been clarified, and the successful use of PD-1 blockers in anticancer therapy eventually led to the development of the current generation of ICIs. Nivolumab was the first ICI approved for treating lung cancer in 2014. Since then, various ICIs such as pembrolizumab, atezolizumab, and durvalumab have been successively introduced into clinical medicine and have shown remarkable efficacy. The introduction of ICIs constituted a major advancement in lung cancer treatment, but disease prognosis continues to remain low. Therefore, new molecular-targeted therapies coupled with existing anticancer drugs and radiotherapy have recently been explored. This review encompasses the current status, challenges, and future perspectives of ICI treatment in lung cancer.

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors for Refractory or Relapsed Advanced Non-Small-Cell Lung Cancer—A Systematic Review and Network Meta-Analysis

“…The molecular basis underlying these findings requires clarification: Cell death caused by systemic anticancer therapy, such as chemotherapy, elicits an inflammatory response that induces the accumulation of activated T cells. Activated T cells are suppressed by cancer cells via PD-L1, which is eliminated by treatment with Niv and Atz, during secondary and subsequent therapies, thereby restoring the anticancer activity of T cells as well as apoptosis of cancer cells [ 1 , 4 , 12 , 34 ]; ( Figure 12 ). These findings explain the process by which treatment response in advanced NSCLC is improved by ICIs, Niv and Atz, in comparison to chemotherapy (Doc), with or without Ram, during second-line and subsequent treatments.…”

“…However, there are reported cases of primary or adaptive resistance to cancer immunotherapeutic agents such as Niv [ 1 , 4 , 6 ]. Moreover, some patients who are resistant to immunotherapy have been reported to respond to a treatment regimen that includes Ram [ 10 ].…”

“…Advances in molecular and immunologic chemotherapies [ 1 , 2 , 3 ] have resulted in the development of novel strategies for lung cancer treatment [ 1 , 2 , 3 , 4 ]. Despite these advances, lung cancer remains a major source of cancer-related death, accounting for 13% of all cancer mortalities, which is attributed to the poor 5-year survival rate (18%) associated with this disease [ 5 ].…”

“…Immunotherapy, including the use of immune checkpoint inhibitors (ICIs), has recently been approved by the FDA for lung cancer treatment and is widely used for this purpose [ 1 , 4 , 12 , 13 ]. Treatment with Niv, Atz, and Pem, in particular, have significantly improved the outcome of NSCLC patients [ 1 , 3 , 4 , 5 , 12 , 13 ].…”

Precision Medicine in Lung Cancer: Challenges and Opportunities in Diagnostic and Therapeutic Purposes

“…In contrast, for small cell lung cancer (SCLC) which represents 15% of all types of lung cancers, there are actually few choices of cancer treatments and no molecularly targeted drug has been approved. In particular, the potential role of PD-1/PD-L1 inhibitors in SCLC has not been yet considered [44]. Recently, the first study analyzing the PD-L1 expression in SCLC has been conducted at Kyoto University Hospital, where the researchers analyzed the immunohistochemical expression of this marker in paraffin blocks from 39 patients affected by SCLC [45].…”