The Hidden Battle Within: How CD70 and CD27 Shape Cancer's Fate

The CD70 and CD27 proteins are key players in the immune system's fight against cancer. They work together to activate and multiply T cells, which are crucial for attacking cancer cells. However, in cancer, this partnership can backfire. Prolonged interaction between CD70 and CD27 can exhaust and even kill T cells, making them ineffective against the tumor. This is a significant problem because CD70 is found on many types of cancer cells, including blood cancers and solid tumors. What's more, factors like low oxygen levels, certain viruses, and changes in cell structure can increase CD70 production. Meanwhile, CD27 on T cells within tumors often marks them as worn out and ineffective, or even as regulatory T cells that suppress the immune response. Given CD70's prevalence on certain cancer cells, researchers have explored various treatments. These include antibody-drug conjugates, CAR T cells, and monoclonal antibodies targeting CD70. While these have shown promise, especially in blood cancers, they come with challenges. Many CD70-targeting treatments also affect healthy, activated T cells. This is because CD70 isn't exclusive to cancer cells. Additionally, chronic CD70-CD27 interaction releases soluble CD27 into the bloodstream. High levels of this soluble CD27 can indicate resistance to certain immunotherapies, such as anti-PD-(L)1 treatments in kidney cancer, melanoma, and lung cancer. However, in melanoma patients treated with a combination of anti-PD-1 and anti-CTLA-4, soluble CD27 levels didn't predict treatment resistance. This suggests that these patients might benefit from this more aggressive therapy. The CD70-CD27 axis presents an intriguing target for cancer immunotherapy. It could serve as a biomarker to guide treatment choices and as a new target for therapies. However, more research is needed to fully understand and harness its potential. One key question is how to target CD70 on cancer cells without harming healthy T cells. Another is how to interpret soluble CD27 levels to inform treatment decisions. As research continues, the CD70-CD27 axis may become a powerful tool in the fight against cancer.