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

• Published in: Cancers 2024-08, Vol.16 (15), p.2684
• Main Authors: Mori, Natsumi, Dorjkhorloo, Gendensuren, Shiraishi, Takuya, Erkhem-Ochir, Bilguun, Okami, Haruka, Yamaguchi, Arisa, Shioi, Ikuma, Komine, Chika, Endo, Mizuki, Seki, Takaomi, Hosoi, Nobuhiro, Nakazawa, Nobuhiro, Shibasaki, Yuta, Okada, Takuhisa, Osone, Katsuya, Sano, Akihiko, Sakai, Makoto, Sohda, Makoto, Yokobori, Takehiko, Shirabe, Ken, Saeki, Hiroshi
• Format: Article
• Language: English
• Subjects: Antibodies; Antigen presentation; B cells; Cancer; Cancer therapies; CD20 antigen; CD3 antigen; CD86 antigen; Cell proliferation; Cells; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Foxp3 protein; Genetic aspects; Germinal centers; Immune response; Infiltration; Inflammation; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoid tissue; Macrophages; Maturity; Medical colleges; Medical prognosis; Medical research; Metastases; Microsatellite instability; Multivariate analysis; Oncology, Experimental; Patients; Prognosis; T cells
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16152684

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.