{Reference Type}: Journal Article {Title}: A Mature Tertiary Lymphoid Structure with a Ki-67-Positive Proliferating Germinal Center Is Associated with a Good Prognosis and High Intratumoral Immune Cell Infiltration in Advanced Colorectal Cancer. {Author}: Mori N;Dorjkhorloo G;Shiraishi T;Erkhem-Ochir B;Okami H;Yamaguchi A;Shioi I;Komine C;Endo M;Seki T;Hosoi N;Nakazawa N;Shibasaki Y;Okada T;Osone K;Sano A;Sakai M;Sohda M;Yokobori T;Shirabe K;Saeki H; {Journal}: Cancers (Basel) {Volume}: 16 {Issue}: 15 {Year}: 2024 Jul 28 {Factor}: 6.575 {DOI}: 10.3390/cancers16152684 {Abstract}: Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC.