The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review

• Published in: Cancers Vol. 16; no. 2; p. 396
• Main Authors: Narvaez, Dana, Nadal, Jorge, Nervo, Adrian, Costanzo, María Victoria, Paletta, Claudio, Petracci, Fernando E, Rivero, Sergio, Ostinelli, Alexis, Freile, Berenice, Enrico, Diego, Pombo, Maria Teresa, Amat, Mora, Aguirre, Edgar Danilo, Chacon, Matias, Waisberg, Federico
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024
• Subjects: Apoptosis; B cells; Biomarkers; Breast cancer; Cancer; Cancer research; Cancer therapies; Cell death; Chemokines; Chemotherapy; Cytokines; Dendritic cells; Diagnosis; Disease; Estrogen receptors; Genes; Health aspects; Immune checkpoint; Immunotherapy; Inflammation; Literature reviews; Lymphatic system; Lymphocytes; Melanoma; Organogenesis; Progesterone; Tumor-infiltrating lymphocytes; Tumors; breast cancer; prognostic factors; lymphocytes; biomarkers; immunotherapy; tertiary lymphoid structures
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16020396

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).