Tertiary Lymphoid Structures in Brain Metastases of Lung Cancer: Prognostic Significance and Correlation With Clinical Outcomes

SHOTA NOHIRA; SHUNICHIRO KURAMITSU; MASASUKE OHNO; MITSUGU FUJITA; KIMIHIRO YAMASHITA; TORU NAGASAKA; SHOICHI HAIMOTO; NORIAKI SAKAKURA; HIROKAZU MATSUSHITA; RYUTA SAITO

doi:10.21873/anticanres.17184

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Figure 1.
Lung cancer-derived brain metastases (BMs) consist of immature tertiary lymphoid structures (TLSs). (A and B) Representative pathological images of TLSs in primary lung cancer and BMs. The sections were stained with CD4 (red), CD20 (brown), and Bcl-6 (green). (A) A TLS in a primary lung cancer. Magnification: 10×, scale bar: 100 μm. (B) A TLS in a BM tissue. Magnification: 20×, scale bar: 50 μm. (C and D) Comparison of the densities of TLSs (C) and tumor-infiltrating lymphocytes (TILs; D) in the primary lung cancers (n=5) and the BMs (n=17). p-Values were determined using the Mann–Whitney U-test. *p<0.05; ***p<0.001.
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Figure 2.
Tertiary lymphoid structure (TLS) density, but not tumor-infiltrating lymphocyte (TIL) density, in brain metastases (BMs) correlates with patients’ survival after surgical resection. Kaplan–Meier plots displaying postoperative overall survival (OS) of the patients with BMs stratified into high- (n=8) and low-density groups (n=9) based on TLS (A) and TIL (B). p-Values were determined by log-rank test. *p<0.05; N.S.: Not significant.
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Figure 3.
Tertiary lymphoid structure (TLS) density in brain metastases (BMs) is a prognostic factor in patients with lung cancer-derived BM independent of Graded prognostic assessment (GPA) index. The cohorts were classified into two groups based on the GPA index for the correlations between the GPA index, an established prognostic index of BMs, and postoperative overall survival (OS) (A). the TLS density of BMs (B), and the TIL density of BMs (C). p-Values were determined using the Mann–Whitney U-test. *p<0.05; N.S.: Not significant.