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New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer

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Abstract

Background

Metabolic information obtained through 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used to evaluate malignancy by calculating the glucose uptake rate, and these parameters play important roles in determining the prognosis of non-small cell lung cancer (NSCLC). The expression of immune-related markers in tumor tissue reflects the immune status in the tumor microenvironment. However, there is lack of reports on the association between metabolic variables and intra-tumor immune markers. Herein, we investigate the correlation between metabolic status on 18F-FDG PET/CT and intra-tumor immunomarkers’ expression in NSCLC patients.

Methods

From April 2008 to August 2014, 763 patients were enrolled in the analysis to investigate the role of maximum standardized uptake value (SUVmax) in lung cancer. One hundred twenty-two tumor specimens were analyzed by immunohistochemistry (IHC) to intra-tumor immune cells and programmed death protein ligand 1(PD-L1) expression on tumor cells. The correlation between metabolic variables and the expression of tissue immune markers were analyzed.

Results

SUVmax values have significant variations in different epidermal growth factor receptor (EGFR) statuses (wild type vs mutant type), high/low neutrophil-to-lymphocyte ratio (NLR) groups, and high/low platelets-to-lymphocyte ratio (PLR) groups (p < 0.001, p < 0.001, p = 0.003, respectively). SUVmax was an independent prognostic factor in lung cancer patients (p = 0.013). IHC demonstrated a statistically significant correlation between SUVmax and the expression of CD8 tumor-infiltrating lymphocytes (p = 0.015), CD163 tumor-associated macrophages (TAMs) (p = 0.003), and Foxp3-regulatory T cells (Tregs) (p = 0.004), as well as PD-1 and PD-L1 (p = 0.003 and p = 0.012, respectively). With respect to patient outcomes, disease stage, BMI, SUVmax, metabolic tumor volume (MTV), TLG (tumor lesion glycolysis), CD163-TAMs, CD11c-dendritic cells (DCs), PD-L1, and Tregs showed a statistically significant correlation with progression-free survival (PFS) (p < 0.001, 0.023, < 0.001, 0.007, 0.005, 0.004, 0.008, 0.048, and 0.014, respectively), and disease stage, SUVmax, MTV, TLG, CD163-TAMs, CD11c-DCs, and PD-L1 showed a statistically significant correlation with overall survival (OS) (p < 0.001, < 0.001, 0.014, 0.012, < 0.001, 0.001, and < 0.001, respectively).

Conclusion

This study revealed an association between metabolic variable and immune cell expression in the tumor microenvironment and suggests that SUVmax on 18F-FDG PET/CT could be a potential predictor for selecting candidates for immunotherapy.

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Abbreviations

NSCLC:

Non-small cell lung cancer

18F-FDG PET/CT:

18F-Flurodeoxyglucose positron emission tomography/computed tomography

TILs:

Tumor-infiltrating lymphocytes

TAMs:

Tumor-associated macrophages

Tregs:

Regulatory T cells

DCs:

Dendritic cells

PD-1:

Programmed death protein 1

IHC:

Immunohistochemistry

SUV:

Standardized uptake value

PFS:

Progression-free survival

OS:

Overall survival

SCC:

Squamous cell carcinoma

ADC:

Adenocarcinoma

NLR:

Neutrophil-to-lymphocyte ratio

PLR:

Platelets-to-lymphocyte ratio

BMI:

Body mass index

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Funding

This work was supported by National Natural Science Funds of China (Nos. 81401887 and 81401888).

Author information

Authors and Affiliations

  1. Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Yang Wang & Xiubao Ren

  2. National Clinical Research Center of Cancer, Tianjin, 300060, China

    Yang Wang, Ning Zhao, Zhanbo Wu, Na Pan, Xuejie Shen, Ting Liu, Feng Wei, Jian You, Wengui Xu & Xiubao Ren

  3. Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China

    Yang Wang, Ning Zhao, Zhanbo Wu, Na Pan, Xuejie Shen, Ting Liu, Feng Wei, Jian You, Wengui Xu & Xiubao Ren

  4. Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, China

    Yang Wang, Ning Zhao, Zhanbo Wu, Na Pan, Xuejie Shen, Ting Liu, Feng Wei & Xiubao Ren

  5. Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, 300060, China

    Yang Wang, Ning Zhao, Zhanbo Wu, Na Pan, Xuejie Shen, Ting Liu, Feng Wei & Xiubao Ren

  6. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Ning Zhao, Zhanbo Wu, Na Pan, Xuejie Shen, Ting Liu & Feng Wei

  7. Department of Thoracic surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Jian You

  8. Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Wengui Xu

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  1. Yang Wang
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Correspondence to Jian You, Wengui Xu or Xiubao Ren.

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Informed consent was obtained from all individual participants included in the study. Written informed obtained from each subject complies with the Declaration of Helsinki. The study was approved by the Ethical Committee of TMUCHI.

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Wang, Y., Zhao, N., Wu, Z. et al. New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging 47, 1127–1136 (2020). https://doi.org/10.1007/s00259-019-04500-7

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