{"title":"Discrepancies in PD-L1 expression, lymphocyte infiltration, and tumor mutational burden in non-small cell lung cancer and matched brain metastases.","authors":"Yanhui Zhang, Runfen Cheng, Tingting Ding, Jianghua Wu","doi":"10.21037/tlcr-24-735","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Differences in the immune microenvironment and responses to immunotherapy may exist between primary non-small cell lung cancer (NSCLC) and brain metastases (BMs). This study aimed to investigate discrepancies in programmed death-ligand 1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLS), and tumor mutational burden (TMB) between matched BMs and primary tumors (PTs) in NSCLC.</p><p><strong>Methods: </strong>Twenty-six pairs of surgically resected BMs and corresponding PTs from NSCLC patients were collected. PD-L1 expression and TILs, including CD8, CD3, CD4, CD20, CD68, and CD21, were analyzed using immunohistochemistry (IHC) and quantitatively assessed through digital image analysis. Whole-exome sequencing (WES) was performed to investigate genomic discrepancies and variations in TMB.</p><p><strong>Results: </strong>The density of PD-L1<sup>+</sup> cells did not differ significantly between matched PTs and BMs (P>0.99). However, BMs exhibited a higher tumor proportion score (TPS) compared to PTs (mean TPS: 31.92% <i>vs.</i> 25.96%, P=0.049), with moderate agreement in categorized TPS (κ=0.653). Analysis of TILs revealed a significant reduction in CD3<sup>+</sup> T cells (P<0.001), CD8<sup>+</sup> cytotoxic T cells (P<0.001), CD20<sup>+</sup> B cells (P<0.001), and CD68<sup>+</sup> macrophages (P=0.02) in BMs compared to PTs. BMs also exhibited a loss of TLS, with no presence of mature TLS marked by CD21 expression. The number of non-synonymous mutations was generally higher in BMs than in PTs, with only 34.69% of mutations shared between paired PTs and BMs. TMB was slightly increased in BMs (mean TMB: 34.2 mutations/Mb in BMs <i>vs.</i> 26.8 mutations/Mb in PTs; P=0.30). Additionally, the log-rank test indicated that a higher density of CD20<sup>+</sup> B cells in BMs was significantly associated with better overall survival (P=0.007).</p><p><strong>Conclusions: </strong>Compared to primary NSCLC tumors, matched BMs show an increase in TPS of PD-L1 expression and TMB, but a significant reduction in TILs and loss of mature TLS, suggesting an immune-suppressive microenvironment in BMs. The infiltration of CD20<sup>+</sup> B cells may serve as a potential prognostic biomarker in NSCLC with BMs.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 12","pages":"3590-3602"},"PeriodicalIF":4.0000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736585/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational lung cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tlcr-24-735","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Differences in the immune microenvironment and responses to immunotherapy may exist between primary non-small cell lung cancer (NSCLC) and brain metastases (BMs). This study aimed to investigate discrepancies in programmed death-ligand 1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLS), and tumor mutational burden (TMB) between matched BMs and primary tumors (PTs) in NSCLC.
Methods: Twenty-six pairs of surgically resected BMs and corresponding PTs from NSCLC patients were collected. PD-L1 expression and TILs, including CD8, CD3, CD4, CD20, CD68, and CD21, were analyzed using immunohistochemistry (IHC) and quantitatively assessed through digital image analysis. Whole-exome sequencing (WES) was performed to investigate genomic discrepancies and variations in TMB.
Results: The density of PD-L1+ cells did not differ significantly between matched PTs and BMs (P>0.99). However, BMs exhibited a higher tumor proportion score (TPS) compared to PTs (mean TPS: 31.92% vs. 25.96%, P=0.049), with moderate agreement in categorized TPS (κ=0.653). Analysis of TILs revealed a significant reduction in CD3+ T cells (P<0.001), CD8+ cytotoxic T cells (P<0.001), CD20+ B cells (P<0.001), and CD68+ macrophages (P=0.02) in BMs compared to PTs. BMs also exhibited a loss of TLS, with no presence of mature TLS marked by CD21 expression. The number of non-synonymous mutations was generally higher in BMs than in PTs, with only 34.69% of mutations shared between paired PTs and BMs. TMB was slightly increased in BMs (mean TMB: 34.2 mutations/Mb in BMs vs. 26.8 mutations/Mb in PTs; P=0.30). Additionally, the log-rank test indicated that a higher density of CD20+ B cells in BMs was significantly associated with better overall survival (P=0.007).
Conclusions: Compared to primary NSCLC tumors, matched BMs show an increase in TPS of PD-L1 expression and TMB, but a significant reduction in TILs and loss of mature TLS, suggesting an immune-suppressive microenvironment in BMs. The infiltration of CD20+ B cells may serve as a potential prognostic biomarker in NSCLC with BMs.
期刊介绍:
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.