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Background <p>The tumor immune microenvironment (TME) of epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) remains poorly characterized. We hypothesized that a higher abundance of tertiary lymphoid structures (TLSs) is associated with improved disease-free survival (DFS) and that TLS abundance differs across major EGFR mutation subtypes.</p> Methods <p>We retrospectively analyzed the medical records of 213 patients with EGFR mutation-positive NSCLC who underwent surgical resection between 2007 and 2015. TLS was defined as the presence of lymphocyte aggregates containing peripheral nodal addressin-positive endothelial venules. Clinicopathological factors, prognosis, and spatial immune profiles were assessed using imaging mass cytometry.</p> Results <p>Tumors with high TLS abundance were more frequent in the L858R than in Exon19del cases (57% vs. 37%, <i>P</i> = 0.011). In stage II–III disease, high TLS abundance remained prognostic (<i>P</i> = 0.003), particularly in L858R tumors. Univariate analysis revealed that TLS abundance is an independent prognostic factor. Imaging mass cytometry showed a higher density of granzyme B-positive cytotoxic lymphocytes in tumors with high TLS abundance.</p> Conclusions <p>Higher TLS abundance was associated with improved DFS in EGFR mutation-positive NSCLC, especially in L858R tumors. TLS abundance may reflect a more active cytotoxic immune niche and contribute to differential therapeutic responses; however, mechanistic interpretations require further validation.</p>

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Tertiary lymphoid structures in the tumor immune microenvironment of EGFR mutation–positive lung cancer are associated with prognosis: a retrospective review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月1日

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  • Hikaru Yamaguchi,
  • Masaru Hisa,
  • Akio Enta,
  • Yoshiyuki Maruya,
  • Kosuke Fujisima,
  • Sho Inomata,
  • Hayato Mine,
  • Hironori Takagi,
  • Yuki Ozaki,
  • Masayuki Watanabe,
  • Takuya Inoue,
  • Takumi Yamaura,
  • Mitsuro Fukuhara,
  • Satoshi Muto,
  • Naoyuki Okabe,
  • Takeo Hasegawa,
  • Kazuyuki Hamada,
  • Jun Osugi,
  • Mika Hoshino,
  • Mitsunori Higuchi,
  • Yutaka Shio,
  • Hiroyuki Suzuki

摘要

Background

The tumor immune microenvironment (TME) of epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) remains poorly characterized. We hypothesized that a higher abundance of tertiary lymphoid structures (TLSs) is associated with improved disease-free survival (DFS) and that TLS abundance differs across major EGFR mutation subtypes.

Methods

We retrospectively analyzed the medical records of 213 patients with EGFR mutation-positive NSCLC who underwent surgical resection between 2007 and 2015. TLS was defined as the presence of lymphocyte aggregates containing peripheral nodal addressin-positive endothelial venules. Clinicopathological factors, prognosis, and spatial immune profiles were assessed using imaging mass cytometry.

Results

Tumors with high TLS abundance were more frequent in the L858R than in Exon19del cases (57% vs. 37%, P = 0.011). In stage II–III disease, high TLS abundance remained prognostic (P = 0.003), particularly in L858R tumors. Univariate analysis revealed that TLS abundance is an independent prognostic factor. Imaging mass cytometry showed a higher density of granzyme B-positive cytotoxic lymphocytes in tumors with high TLS abundance.

Conclusions

Higher TLS abundance was associated with improved DFS in EGFR mutation-positive NSCLC, especially in L858R tumors. TLS abundance may reflect a more active cytotoxic immune niche and contribute to differential therapeutic responses; however, mechanistic interpretations require further validation.