Dr. Steven A. Greenberg from Harvard Medical School, a leading researcher in cancer immunotherapy, discusses a groundbreaking discovery on the relationship between immune proteins KLRG1 and PD-1. He highlights how this connection could explain the varying effectiveness of current treatments and suggests new strategies to combine therapies for improved outcomes. The conversation explores the immune system's battle against cancer and how targeting both KLRG1 and PD-1 might revolutionize treatment options for patients facing challenging cancers.
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insights INSIGHT
KLRG1 and PD-1: A Surprising Relationship
KLRG1 and PD-1, two immune system proteins, show an unexpected link.
This discovery may explain why some cancer immunotherapies are less effective.
insights INSIGHT
How Cancer Evades the Immune System
Cancer can evade the immune system by manipulating immune checkpoints like PD-1.
PD-1 inhibitors block this "off switch" and help T cells stay active.
insights INSIGHT
Limitations of PD-1 Immunotherapy
PD-1 inhibitors have limitations; some patients don't respond or have short-term benefits.
Combining PD-1 inhibitors with other therapies often yields only additive, not synergistic, effects.
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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).
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