Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Tertiary lymphoid structures (TLS) are associated with anti-tumor immunity and prognosis in colorectal cancer.
• The role of TLS in rectal adenocarcinoma and its interaction with neoadjuvant therapies (neoTx) are not well understood.

Purpose of the Study:

• To investigate the impact of TLS on the immune microenvironment of locally advanced rectal cancer (LARC).
• To explore the relationship between TLS and response to neoTx in LARC patients.

Main Methods:

• Hematoxylin-eosin staining, immunohistochemistry, and biomolecular analyses were performed.
• TLS and tumor-infiltrating lymphocytes (TILs) were analyzed in 221 neoTx-treated and 242 treatment-naïve LARC patients.
• TLS density, maturity, and immune cell infiltration were assessed.

Main Results:

• High TLS density correlated with favorable clinicopathological features, longer recurrence-free survival (RFS), and increased adaptive immune cell infiltration.
• A high TLS-score was linked to greater immune cell infiltration and activated immune-related pathways.
• TLS-positive tumors showed significantly higher response rates and pathological complete remission (pCR) after neoTx, with improved RFS.
• NeoTx decreased TLS density and maturity, diminishing the prognostic significance of TLS.

Conclusions:

• TLS plays a key role in mediating a T-cell-inflamed tumor microenvironment in LARC.
• TLS presence before treatment predicts a better response to neoTx and improved survival outcomes.
• NeoTx negatively impacts TLS, suggesting potential for novel therapeutic strategies, particularly neoadjuvant immunotherapy, in LARC.