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Neoadjuvant Chemoimmunotherapy Increases Tumor Immune Lymphocytes Infiltration in Resectable Non-small Cell Lung Cancer

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Neoadjuvant chemoimmunotherapy treatment (NCIT) has achieved great success for non-small cell lung cancer (NSCLC); however, the intrinsic mechanism underlying this treatment remains unclear.

Methods

Thirty-two patients with stage IIA–IIIC NSCLC who underwent surgery after NCIT were included in this retrospective study. Multiplex immunofluorescence (mIF) staining and image analysis assays were performed on the samples collected before and after NCIT for each patient. RNA analyses was applied to confirm the mIF results.

Results

Among the enrolled patients, 14 achieved major pathological response or pathological complete response (pCR) and were defined as the ‘response’ group, whereas 18 patients did not respond well to NCIT and were defined as the ‘nonresponse’ group. The results of the mIF assays revealed an overall increase in tumor immune lymphocytes (TILs) after NCIT in the stroma area (p = 0.03) rather than the tumor area (p = 0.86). The percentage of CD8+ T cells and tertiary lymphoid structure counts in both the response and nonresponse groups increased significantly after NCIT compared with before NCIT. CD3+ T cells and FOXP3+ cells decreased significantly in the response group but remained unchanged or increased in the nonresponse group. A comparison of the response and nonresponse groups showed that CD3, FOXP3+ and CD8+/PD-1+ cells before NCIT may serve as predictors of the response to neoadjuvant immunotherapy. The RNA analyses confirmed the mIF results that TILs were elevated after NCIT.

Conclusions

The infiltration of immune cells before NCIT was correlated with pathologic complete response, which enhanced the TILs as a promising predictor for selecting patients who were more likely to benefit from NCIT.

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Data Availability

Sequence Archive for National Genomics Data Center (BioProject ID: PRJCA013526, https://ngdc.cncb.ac.cn/bioproject/browse/PRJCA013526; OMIX ID: OMIX002464, https://ngdc.cncb.ac.cn/omix/release/OMIX002464). The data generated and analyzed during this study are described in the ESM (Tables S1 and S2).

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Acknowledgments

This study was funded by the National Natural Science Foundation of China (82072564, 82272679), Project of Shanghai Natural Science Foundation (20ZR1452000), Program of Shanghai Academic Research Leader (22XD142280), Shanghai Municipal Health Commission (2022XD029), Shanghai Youth Talent Support Program, Shanghai Talent Development Fund (2019073), Shanghai Chest Hospital Project of Collaborative Innovative Grant (YJT20190209), The Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212302), Lian Yun Gang Shi Hui Lan Public Foundation (HL-HS2020-65), Guangdong Association of Clinical Trials (GACT)/Chinese Thoracic Oncology Group (CTONG) and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (2017B030314120), National Multi-disciplinary Treatment Project for Major Diseases (2020NMDTP), and Shanghai Chest Hospital Project of Talent Support (2018YNZYJ02)

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Author notes

  1. Tianxiang Chen and Zhengqi Cao have contributed equally to this work.

Authors and Affiliations

  1. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

    Tianxiang Chen MD, Zhengqi Cao MD, Yingjia Sun MD, Jia Huang MD, Shengping Shen MD, Yueping Jin MD, Long Jiang MD, Shun Lu MD & Ziming Li MD

  2. The Medical Department, 3D Medicines Inc., Shanghai, China

    Fengcai Wen MD, Xiaochen Zhao MD, Ding Zhang MD, Yanan Chen MD, Mengli Huang MD & Hao Chen MD

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Contributions

TC and ZC contributed equally to this work. YS, JH, SS, SL and ZL participated in the design and performance of this study. FW, XZ and DZ participated in the analysis and interpretation of the data. YC, HC and MH performed the statistical analysis. The manuscript was drafted by TC, FW and DZ, and was reviewed by all authors. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shun Lu MD or Ziming Li MD.

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Disclosures

Fengcai Wen, Xiaochen Zhao, Ding Zhang, Mengli Huang, Yanan Chen, and Hao Chen were employed by 3D Medicines-Shanghai Inc. Tianxiang Chen, Zhengqi Cao, Yingjia Sun, Jia Huang, Shengping Shen, Yueping Jin, Long Jiang, Shun Lu, and Ziming Li declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Chen, T., Cao, Z., Sun, Y. et al. Neoadjuvant Chemoimmunotherapy Increases Tumor Immune Lymphocytes Infiltration in Resectable Non-small Cell Lung Cancer. Ann Surg Oncol 30, 7549–7560 (2023). https://doi.org/10.1245/s10434-023-14123-w

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