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Exploring the impact of tertiary lymphoid structures maturity in NSCLC: insights from TLS scoring. | LitMetric

AI Article Synopsis

  • Tertiary Lymphoid Structures (TLS) are linked to better cancer patient survival and responses to immunotherapies, but their effectiveness can vary based on size, composition, and maturation.
  • A study on Non-Small Cell Lung Carcinoma (NSCLC) used a multiplex immunofluorescent panel to analyze tumor samples from 406 patients, focusing on specific immune cell types within TLS.
  • The analysis led to a TLS scoring system that identified key features predictive of patient outcomes, showing correlations with other cancer biomarkers but not with PD-L1 status.

Article Abstract

Tertiary Lymphoid Structures (TLS) are lymphoid structures commonly associated with improved survival of cancer patients and response to immunotherapies. However, conflicting reports underscore the need to consider TLS heterogeneity and multiple features such as TLS size, composition, and maturation status, when assessing their functional impact. With the aim of gaining insights into TLS biology and evaluating the prognostic impact of TLS maturity in Non-Small Cell Lung Carcinoma (NSCLC), we developed a multiplex immunofluorescent (mIF) panel including T cell (CD3, CD8), B cell (CD20), Follicular Dendritic cell (FDC) (CD21, CD23) and mature dendritic cell (DC-LAMP) markers. We deployed this panel across a cohort of primary tumor resections from NSCLC patients (N=406) and established a mIF image analysis workstream to specifically detect TLS structures and evaluate the density of each cell phenotype. We assessed the prognostic significance of TLS size, number, and composition, to develop a TLS scoring system representative of TLS biology within a tumor. TLS relative area, (total TLS area divided by the total tumor area), was the most prognostic TLS feature (C-index: 0.54, p = 0.04). CD21 positivity was a marker driving the favorable prognostic impact, where CD21 CD23 B cells (C-index: 0.57, p = 0.04) and CD21 CD23 FDC (C-index: 0.58, p = 0.01) were the only prognostic cell phenotypes in TLS. Combining the three most robust prognostic TLS features: TLS relative area, the density of B cells, and FDC CD21 CD23 we generated a TLS scoring system that demonstrated strong prognostic value in NSCLC when considering the effect of age, sex, histology, and smoking status. This TLS Score also demonstrated significant association with Immunoscore, EGFR mutational status and gene expression-based B-cell and TLS signature scores. It was not correlated with PD-L1 status in tumor cells or immune cells. In conclusion, we generated a prognostic TLS Score representative of the TLS heterogeneity and maturity undergoing within NSCLC tissues. This score could be used as a tool to explore how TLS presence and maturity impact the organization of the tumor microenvironment and support the discovery of spatial biomarker surrogates of TLS maturity, that could be used in the clinic.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457083PMC
http://dx.doi.org/10.3389/fimmu.2024.1422206DOI Listing

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