Cytosolic high-mobility group box protein 1 (HMGB1) and/or PD-1+ TILs in the tumor microenvironment may be contributing prognostic biomarkers for patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.

Rectal cancer, which comprises 30% of all colorectal cancer cases, is one of the most common forms of cancer in the world. Patients with locally advanced rectal cancer (LARC) are often treated with neoadjuvant chemoradiotherapy (neoCRT) followed by surgery. However, after neoCRT treatment, approximately one-third of the patients progress to local recurrence or distant metastasis. In these studies, we found that patients with tumors that exhibited cytosolic HMGB1(Cyto-HMGB1) translocation and/or the presence of PD-1+ tumor-infiltrating lymphocytes (TILs) before treatment had a better clinical outcome. The better outcome is likely due to the release of HMGB1, which triggers the maturation of dendritic cells (DCs) via TLR4 activation, and the subsequent recruitment of PD-1+ tumor-infiltrating lymphocytes to the tumor site, where they participate in immune-scavenging. In conclusion, our results provide evidence that cyto-HMGB1 and/or PD-1+TIL are not only predictive biomarkers before treatment, but they can also potentially designate patients for personalized oncological management including immunotherapy.