An unexpected link between KLRG1 and PD-1, two key immune system proteins, was revealed in a study recently published in Oncotarget. This discovery could help explain why some cancer immunotherapy treatments are less effective for certain patients and lead to new therapeutic strategies. How the Immune System Fights Cancer The immune system is a powerful defense mechanism against cancer, with CD8 T cells acting as the primary soldiers. These specialized immune cells identify and destroy tumor cells. However, cancer can cleverly evade this attack by manipulating immune checkpoints—natural “breaks” on the immune system that prevent it from overreacting and damaging healthy tissue. One of the most studied checkpoints is PD-1 (Programmed Death-1), a receptor on T cells that acts as an “off switch” when activated by tumor cells. This mechanism suppresses the immune response, allowing cancer to grow without control. In response, researchers have developed treatments called PD-1 inhibitors, which block this “off switch” and keep T cells active. The Study: Investigating KLRG1 and PD-1 in Tumor-Fighting T Cells In the study titled “Anti-correlation of KLRG1 and PD-1 expression in human tumor CD8 T cells,” Dr. Steven A. Greenberg from Harvard Medical School analyzed publicly available gene expression data from various cancer types, including lung cancer, melanoma, and colorectal cancer. His goal was to identify immune-related proteins that could complement existing therapies, such as PD-1 inhibitors. Full blog - https://www.oncotarget.org/2025/01/28/a-new-approach-for-cancer-treatment-the-surprising-relationship-between-klrg1-and-pd-1/ Paper DOI - https://doi.org/10.18632/oncotarget.28679 Correspondence to - Steven A. Greenberg - sagreenberg@bwh.harvard.edu Video short - https://www.youtube.com/watch?v=PME2xfyYN18 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28679 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, immunotherapy, KLRG1 About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM