Abstract
Immune checkpoint blockade (ICB) immunotherapy induces potent antitumor immunity across multiple solid tumors, although few patients respond well to this therapy. An emerging biomarker for predicting responsiveness to ICB immunotherapy is tumor mutational burden (TMB). Although several surrogate biomarkers, including deficient mismatch repair, TP53/KRAS mutations, and comutations in DNA damage response pathways, have been shown to be effective for predicting the response to checkpoint blockade immunotherapy, each is positive for only a small cohort of candidates, and many potential responders to ICB are inevitably missed. Here, we found that titin (TTN), which is frequently detected in solid tumors, is associated with increased TMB and correlated with objective response to ICB. In 7 public clinical cohorts, all patients with mutated TTN showed longer progression-free survival or overall survival than those with wild-type status. Furthermore, an improved objective response rate and higher TMB were identified in cohorts with accessible information. Identification of TTN mutation as a predictor of improved outcomes in response to ICBs provides a clinically feasible assessment for estimating TMB and ICB therapy outcomes.
Authors
Qingzhu Jia, Jun Wang, Ning He, Ji He, Bo Zhu
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
