Ding GY, Ma JQ, Yun JP, et al. - Researchers aimed at determining the prognostic value and relevant mechanisms of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA).

• A total of 962 patients from three cancer centers were retrospectively included.

• Researchers established a quaternary TLS scoring system for intra-tumor region (T score) and peri-tumor region (P score), respectively.

• There appeared a positive correlation of T score with favorable prognosis, whereas a worse survival was recorded in correlation with a high P score; suggesting opposite prognostic impacts of TLSs located within or outside the tumor region.

• Possibly the functional state of TLSs is determined by the heterogeneous distribution of Tfh and Treg cells within the spatially different TLSs.

• The integrated analysis of TLSs led to stratification of iCCAs into four immune subclasses with distinct clinical outcomes.

• The risk appeared lowest for patients with an immune active pattern, with 5-year OS rates of 68.8%, whereas survival at 5 years was recorded for only 3.4% of patients with immune excluded pattern.