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Distinct cellular immune profiles in lung adenocarcinoma manifesting as pure ground glass opacity versus solid nodules

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Abstract

Introduction

Ground glass opacity featured lung adenocarcinomas (GGO-LUAD) display more indolent biological behavior than solid nodule featured lung adenocarcinomas (SN-LUAD) and have an excellent prognosis. However, the cellular immune characteristics of GGO-LUAD remain poorly understood.

Methods

Immunohistochemistry technique was performed to stain related immune markers (CD8, CD103, CD20, CD138, CD4, FOXP3, CD68, CD163, PD-1 and PD-L1) and TGF-β from 15 patients with pure GGO-LUAD and 15 patients with SN-LUAD tissue sections (Paired cohort), and then, the related markers with significant differences were verified on 10 patients (Verified cohort) with both pure GGO-LUAD and SN-LUAD. For localization analysis of CD68 + tumor-associated macrophages (TAMs) and FOXP3 + Terg cells in tumor areas, pure GGO-LUAD and SN-LUAD were also stained for simultaneous detection of pan-CK, CD68 and FOXP3 by multiplex immunofluorescence.

Results

In the Paired cohort, compared with SN-LUAD, only the infiltration of TAMs and Treg cells was significantly lower in GGO-LUAD. The infiltration of the remaining immune cells including CD8 + T cells, CD4 + T cells, CD103 + T cells, CD20 + B cells and CD138 + Plasma cells in GGO-LUAD, although relatively low, was not significantly different. Meanwhile, the expression of TGF-β was significantly higher in SN-LUAD. And the above results have also been confirmed in the Verified cohort. Moreover, there was no significantly difference in PD-L1 expression in GGO-LUAD compared to SN-LUAD both in the Paired cohort and Verified cohort.

Conclusions

GGO-LUAD demonstrates an overall less active immune landscape as compared with SN-LUAD. TAMs and TGF-β may play an important role in the progression of GGO-LUAD. More importantly, PD-L1 expression in GGO-LUAD is comparable to that in SN-LUAD, indicating that there may be other reasons for the insensitivity of GGO-LUAD to immunotherapy.

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Data availability

The dataset used for this study is available from the corresponding author upon reasonable request.

Abbreviations

GGO-LUAD:

Ground glass opacity featured lung adenocarcinomas

SN-LUAD:

Solid nodule featured lung adenocarcinomas

TAMs:

Tumor-associated macrophages

LDCT:

Low-dose computed tomography

HRCT:

High-resolution computed tomography

FFPE:

Formalin-fixed, paraffin-embedded

OS:

Overall survival

AAH:

Atypical adenomatous hyperplasia

AIS:

Adenocarcinoma in situ

MIA:

Minimally invasive adenocarcinoma

IAC:

Invasive lung adenocarcinoma

TME:

The tumor microenvironment

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Acknowledgements

We thank all the contributing authors for their great effort on this article and greatly appreciate all patients who contributed to this study.

Funding

The study is funded by the Tongji Hospital Clinical Research Flagship Program (No.2019CR107). The funding sources had no influence on the analysis and interpretation of data or on the contents of the manuscript.

Author information

Authors and Affiliations

  1. Thoracic Surgery Laboratory, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China

    Rirong Qu, Fan Ye, Shaojie Hu, Boyu Wang, Xiangning Fu, Lequn Li & Yixin Cai

  2. Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Shenghui Qin & Jing Xiong

Authors
  1. Rirong Qu
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  2. Fan Ye
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  3. Shaojie Hu
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  4. Boyu Wang
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  5. Shenghui Qin
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  7. Xiangning Fu
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  8. Lequn Li
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  9. Yixin Cai
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Contributions

RQ: conceptualization, data curation, formal analysis, software, investigation, methodology, supervision, visualization, roles/writing—original draft, writing—review and editing. FY: data curation, formal analysis, software, writing—review and editing. SH: data curation and investigation. BW: data curation and methodology. SQ: data curation, formal analysis, project administration and visualization. JX: data curation, project administration and visualization. XF: data curation, formal analysis, investigation, writing—review and editing. LL: data curation, formal analysis, investigation, validation, visualization, writing—review and editing. YC: Conceptualization, Data curation, Formal analysis, Investigation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Roles/Writing—original draft, Writing—review & editing.

Corresponding author

Correspondence to Yixin Cai.

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The authors declare that they have no competing interests.

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Informed consent was obtained from all individual participants included in the study.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approvals were obtained by the institutional review board of Tongji Medical College of Huazhong University of Science and Technology.

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Qu, R., Ye, F., Hu, S. et al. Distinct cellular immune profiles in lung adenocarcinoma manifesting as pure ground glass opacity versus solid nodules. J Cancer Res Clin Oncol 149, 3775–3788 (2023). https://doi.org/10.1007/s00432-022-04289-3

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