Advances in Immune Checkpoint Inhibitors for Cancer Treatment
Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(11), 1804; https://doi.org/10.3390/cancers18111804
Submission received: 21 April 2026
/
Revised: 22 May 2026
/
Accepted: 25 May 2026
/
Published: 1 June 2026
(This article belongs to the Special Issue Cancer Inhibitory Receptors and Related Cancer Immunotherapy)
Simple Summary
Tumor cells evade attack by the immune system through immune checkpoint proteins, making these proteins important targets in cancer immunotherapy. By targeting them, immune checkpoint inhibitors (ICIs) help restore the body’s antitumor response by reactivating immune cells suppressed in the tumor microenvironment. This review summarizes well-known immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4, as well as emerging checkpoints like LAG-3, TIM-3, TIGIT, BTLA, SIRP-α, CD200, ILT4, and CD24, together with recent clinical advances. It also explains why some patients develop resistance to these treatments and explores future strategies to improve their effectiveness in cancer therapy.
Abstract
The discovery of immune checkpoint proteins has marked a major breakthrough in cancer immunotherapy. During cancer development and progression, tumor cells exploit multiple immune checkpoint pathways to evade immune surveillance. Immune checkpoint inhibitors (ICIs) have been developed to restore antitumor immunity by reactivating immune cells that are functionally suppressed within the tumor microenvironment. This review provides a comprehensive overview of the regulation and therapeutic targeting of immune checkpoint proteins in cancer, covering both classical checkpoints, including PD-1, PD-L1, and CTLA-4, and emerging targets such as LAG-3, TIM-3, TIGIT, BTLA, SIRP-α, CD200, ILT4, and CD24. In addition, we summarize current clinical advances and the therapeutic potential of approved and investigational ICIs, examine the mechanisms underlying ICI resistance, and discuss future strategies to overcome resistance, highlighting the mechanisms of action and their implications for future cancer treatment.
