Peritumoral tertiary lymphoid structure and tumor stroma percentage predict the prognosis of patients with non-metastatic colorectal cancer

Abstract

Background: Tertiary lymphoid structures (TLSs) are crucial in promoting and maintaining positive anti-tumor immune responses. The tumor stroma has a powerful immunosuppressive function that could exclude tumor-infiltrating lymphocytes from the tumor beds and lead to a "cold" phenotype. TLSs and tumor stroma percentage (TSP) are significantly associated with the prognosis of patients with certain cancers. However, the exact roles of TLSs and TSP and their intrinsic relationship are still largely unknown in colorectal cancer (CRC).Methods: TLSs and TSP were assessed using hematoxylin-eosin (H&E) and/or immunohistochemistry (IHC) staining from 114 CRC patients in the training set and 60 CRC patients in the external validation set. The correlation between TILs, TLS and clinicopathological characteristics and their prognostic values were assessed. Finally, we plotted a Nomogram including the TLS, TSP and tumor-node-metastasis (TNM) stage to predict the probability of recurrencefree survival (RFS) at 2-and 5-years in non-metastatic colorectal cancer (nmCRC) patients.Results: Peritumoral TLS (P-TLS), intratumoral TLS (In-TLS) and high TSP (H-TSP, >50%) were present in 99.1%, 26.3% and 41.2% patients, respectively. H-TSP tumor tends to be associated with lower P-TLS density (P =0.0205). The low P-TLS density (< 0.098/mm 2 ) was significantly associated with reduced RFS (HR=6.597 95% CI: 2.882-15.103, P <0.001) and reduced overall survival (OS) (HR=6.628 95% CI: 2.893-15.183, P < 0.001) of nmCRC patients. In-TLS was not of significance in evaluating the clinical outcomes of nmCRC patients. H-TSP was significantly associated with reduced RFS (HR=0.126 95%

The Prognostic Significance of Tertiary Lymphoid Structure Assessment with Hematoxylin and Eosin Sections in Esophageal Squamous Cell Carcinoma

“…Thus, our practice proved that H&E section assessment is very potential in ESCC for TLS evaluation and prognostic prediction. However, the density and diameter pro les showed certain association with overall survival both in our and TCGA datasets, they can't be used as predictive biomarkers in ESCC, which is unlike that in gastric cancer (Kemi et al 2023) and colorectal carcinoma (Wang et al 2022a). This divergence underscores the inherent heterogeneity prevalent across various cancer types.…”

Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

“…We found that CD20 B cells and CD3 T cells were the major cell types within these patches, indicating their lymphoid origin (Fig S5E,F). Peritumoral structures have condensed B cells follicles surrounded by T cells and high endothelial vessels (HEV), confirming that these are primary follicular TLSs 71,72 . Distant lymphoid structures in the mucosal layer have a more dispersed and intermixed T and B-cell distribution, indicating a lower degree of maturation.…”

Infiltrating characteristics and prognostic value of tertiary lymphoid structures in resected gastric neuroendocrine neoplasm patients

“…Initially, all available H&E‐stained sections in the training set were reviewed. Tumor‐related TLS was defined to be within 7 mm of the tumor border, including the tumor region based in line with previous findings 31,37 . We only included specimens containing both tumor tissue and surrounding para‐tumor tissue in this study.…”

“…TLS is a protective predictor of prognosis in tumors such as breast cancer, 17 lung cancer, 18,19 colorectal cancer, 20 malignant melanoma, 21 ovarian cancer, 22 gastric cancer, 23 pancreatic cancer, 24 and oral squamous cell carcinoma 25 . TLS is also associated with a favorable prognosis in most gastrointestinal tumors 26–31 . In addition, TLS might serve as a compartment for generating memory T and B cells, enhancing the anti‐tumor immune response 32 .…”

“…25 TLS is also associated with a favorable prognosis in most gastrointestinal tumors. [26][27][28][29][30][31] In addition, TLS might serve as a compartment for generating memory T and B cells, enhancing the anti-tumor immune response. 32 Although most studies reported that the presence of TLS is associated with good patient survival, [17][18][19][20][21][22][23][24][25] Finkin et al 33 concluded that the presence of TLS was a poor prognostic factor for hepatocellular carcinoma (HCC).…”