Submit a comment
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
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
