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The predictive value of inflammatory biomarkers for major pathological response in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy and its association with the immune-related tumor microenvironment: a multi-center study

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A Correction to this article was published on 20 September 2022

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Abstract

Background

Inflammatory biomarkers in the peripheral blood have been established as predictors for immunotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC). Whether they can also predict major pathological response (MPR) in neoadjuvant setting remains unclear.

Methods

In this multi-center retrospective study, 122 and 92 stage I-IIIB NSCLC patients from six hospitals who received neoadjuvant chemoimmunotherapy followed by surgery were included in the discovery and external validation cohort, respectively. Baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) were calculated and associated with MPR. Furthermore, resected tumor samples from 37 patients were collected for RNA-sequencing to investigate the immune-related tumor microenvironment.

Results

In both the discovery and validation cohorts, the on-treatment NLR, dNLR, PLR, and SII levels were significantly lower in the patients with MPR versus non-MPR. On-treatment SII remained an independent predictor of MPR in multivariate logistic regression analysis. The area under the curve (AUC) of on-treatment SII for predicting MPR was 0.75 (95%CI, 0.67–0.84) in the discovery cohort. Moreover, the predictive value was further improved by combining the on-treatment SII and radiological tumor regression data, demonstrating an AUC of 0.82 (95%CI, 0.74–0.90). The predictive accuracy was validated in the external cohort. Compared with the SII-high group, patients with SII-Low were associated with the activated B cell receptor signaling pathway and a higher intratumoral immune cell infiltration level.

Conclusions

On-treatment SII was independently associated with MPR in NSCLC patients receiving neoadjuvant chemoimmunotherapy. Further prospective studies are warranted.

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Data availability

The data that support the finding of our study are available on request from the corresponding author.

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Acknowledgements

We ae grateful to all the members in the multidisciplinary team for their efforts.

Funding

This study was supported by National Key Research and Development Program of China (2021YFC2500904 and 2021YFC2500905), Shanghai Municipal Health Commission (202040322, 201940192, 2019SY072), Shanghai Hospital Development Center (SHDC22021217), National Natural Science Foundation of China (No. 81972176), and the Science Foundation of Shanghai (No.18ZR1435100).

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Author notes

  1. Chongwu Li, Junqi Wu and Long Jiang have contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China

    Chongwu Li, Junqi Wu, Lei Zhang, Yue Zhao, Xiucheng Liu, Lang Xia, Haoran E, Peigen Gao, Yunlang She, Dong Xie & Chang Chen

  2. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

    Long Jiang, Jia Huang, Yu Tian & Qingquan Luo

  3. Department of Pathology, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China

    Likun Hou

  4. Department of Thoracic Surgery, Ningbo No. 2 Hospital, Chinese Academy of Sciences, Zhejiang, People’s Republic of China

    Minglei Yang

  5. Department of Thoracic Surgery, The First Hospital of Lanzhou University, Gansu, People’s Republic of China

    Minjie Ma

  6. Department of Oncology, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China

    Chunxia Su

  7. Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, Jiangsu, People’s Republic of China

    Hao Zhang

  8. Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China

    Hezhong Chen

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  1. Chongwu Li
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Contributions

The study conducts and design: CL, JW, LJ, and LZ, QL, and CC; data acquisition: CL, JW, JH, YT, XL, LX, LH, MY, MM, CS, HZ, and HC; data analysis and interpretation: CL, JW, LJ, YZ, HE, PG, YS, and DX; drafting the manuscript or revising it: all authors; final approval of the manuscript: all authors.

Corresponding authors

Correspondence to Dong Xie, Qingquan Luo or Chang Chen.

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The authors declare no competing interests.

Ethics Approval

This study was approved by the Institutional Review Board of Shanghai Pulmonary Hospital (IRB number: L21-224). The IRB waived the patient’s informed consent as this was a non-interventional study using routinely collected data.

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The original online version of this article was revised: Only Dong Xie is listed as the corresponding author. Authors Qingquan Luo (luoqingquan@hotmail.com) and Chang Chen (chenthoracic@163.com) should be listed as well.

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Li, C., Wu, J., Jiang, L. et al. The predictive value of inflammatory biomarkers for major pathological response in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy and its association with the immune-related tumor microenvironment: a multi-center study. Cancer Immunol Immunother 72, 783–794 (2023). https://doi.org/10.1007/s00262-022-03262-w

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