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The clinical significance of tertiary lymphoid structure and its relationship with peripheral blood characteristics in patients with surgically resected non-small cell lung cancer: a single-center, retrospective study

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Abstract

Introduction

The presence of tertiary lymphoid structure (TLS) in tumor tissues has been reported to be a factor associated with a good prognosis in several types of cancers. However, the relationship between TLS formation and peripheral blood findings remains unclear. The purposes of the study were to evaluate the effect of the presence of TLS on survival and determine the peripheral blood characteristics associated with TLS formation in non-small cell lung cancer (NSCLC) patients.

Methods

A total of 147 consecutive NSCLC patients who underwent lung resection at Fukushima Medical University Hospital between 2013 and 2017 were enrolled. TLS expression was evaluated, and the relationships between clinical parameters and outcomes were analyzed. Peripheral blood mononuclear cells (PBMCs) were further analyzed by mass cytometry to characterize the TLS-positive microenvironment.

Results

Forty-six patients had high TLS expression, and the remaining 101 patients had low TLS expression. In stage II to IV patients (n = 35), disease-free survival was longer in the high TLS expression group (p = 0.027). A low neutrophil to lymphocyte ratio (NLR) < 2.75 in the peripheral blood was associated with high TLS expression (p = 0.003). Citrus analysis after mass cytometry assay showed that the number of cells expressing HLA-DR and CD9 in PBMCs was lower in the high TLS expression group.

Conclusion

High TLS expression is associated with a good prognosis after surgery in stage II and III NSCLC patients. In the peripheral blood, a low NLR and few antigen-presenting cells indicate the presence of TLS in the tumor microenvironment.

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Abbreviations

HEV:

High endothelial venule

ICI:

Immune checkpoint inhibitor

NLR:

Neutrophil to lymphocyte ratio

NSCLC:

Non-small cell lung cancer

PD-L1:

Programmed cell death-ligand 1

PNAd:

Peripheral node addressin

TIL:

Tumor-infiltrating lymphocyte

TLS:

Tertiary lymphoid structure

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Acknowledgements

The authors would like to thank Ms. Eiko Ohtomo, Ms. Mie Ohtsuki, and Ms. Yukiko Kikuta (Department of Chest Surgery, Fukushima Medical University, Japan) for their technical assistance.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or non-for-profit sectors.

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Authors and Affiliations

  1. Department of Chest Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan

    Mitsuro Fukuhara, Satoshi Muto, Sho Inomata, Hikaru Yamaguchi, Hayato Mine, Hironori Takagi, Yuki Ozaki, Masayuki Watanabe, Takuya Inoue, Takumi Yamaura, Naoyuki Okabe, Yuki Matsumura, Takeo Hasegawa, Jun Osugi, Mika Hoshino, Mitsunori Higuchi, Yutaka Shio & Hiroyuki Suzuki

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  1. Mitsuro Fukuhara
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Contributions

MF, SM and HS contributed to the study conception and design. Material preparation and data collection were performed by MF, SM, SI, HY, HM, HT, YO, MW, TI, TY, NO, YM, TH, JO, MH, MH and YS. Data analysis was performed by MF and SM. The first draft of the manuscript was written by MF. Review and editing were performed by SM and HS. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Satoshi Muto.

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The authors declare that they have no competing interests.

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Written, informed consent was obtained from all participants.

Ethical approval

This study was approved by the Human Ethics Committee at Fukushima Medical University (approval no. 30161).

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Fukuhara, M., Muto, S., Inomata, S. et al. The clinical significance of tertiary lymphoid structure and its relationship with peripheral blood characteristics in patients with surgically resected non-small cell lung cancer: a single-center, retrospective study. Cancer Immunol Immunother 71, 1129–1137 (2022). https://doi.org/10.1007/s00262-021-03067-3

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