Tertiary lymphoid structures in the tumor immune microenvironment of EGFR mutation-positive lung cancer are associated with prognosis: a retrospective review.
- 1Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan. [email protected].
- 2Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.
Abstract
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.
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BibTeX
@article{yamaguchi2026tertiary,
title = {{Tertiary lymphoid structures in the tumor immune microenvironment of EGFR mutation-positive lung cancer are associated with prognosis: a retrospective review.}},
author = {Hikaru Yamaguchi and Masaru Hisa and Akio Enta and Yoshiyuki Maruya and Kosuke Fujisima and Sho Inomata and Hayato Mine and Hironori Takagi and Yuki Ozaki and Masayuki Watanabe and Takuya Inoue and Takumi Yamaura and Mitsuro Fukuhara and Satoshi Muto and Naoyuki Okabe and Takeo Hasegawa and Kazuyuki Hamada and Jun Osugi and Mika Hoshino and Mitsunori Higuchi and Yutaka Shio and Hiroyuki Suzuki},
journal = {BMC cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16644-5},
url = {https://europepmc.org/article/MED/42958137},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tertiary lymphoid structures in the tumor immune microenvironment of EGFR mutation-positive lung cancer are associated with prognosis: a retrospective review.
AU - Hikaru Yamaguchi
AU - Masaru Hisa
AU - Akio Enta
AU - Yoshiyuki Maruya
AU - Kosuke Fujisima
AU - Sho Inomata
AU - Hayato Mine
AU - Hironori Takagi
AU - Yuki Ozaki
AU - Masayuki Watanabe
AU - Takuya Inoue
AU - Takumi Yamaura
AU - Mitsuro Fukuhara
AU - Satoshi Muto
AU - Naoyuki Okabe
AU - Takeo Hasegawa
AU - Kazuyuki Hamada
AU - Jun Osugi
AU - Mika Hoshino
AU - Mitsunori Higuchi
AU - Yutaka Shio
AU - Hiroyuki Suzuki
PY - 2026
DA - 2026/08/01
JO - BMC cancer
DO - 10.1186/s12885-026-16644-5
UR - https://europepmc.org/article/MED/42958137
AB - 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.
SN - 1471-2407
ER -