Abstract
Purpose
To determine whether TCF-1+PD-1+CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer (NSCLC) patients.
Methods
We investigated the expression of TCF-1+PD-1+CD8+T cells and elucidated their predictive role in NSCLC patients. Pretreatment specimens from 20 advanced NSCLC patients who underwent PD-1 immunotherapy or combined with chemotherapy were analyzed. The frequencies of TCF-1+ cells in PD-1+CD8+T cells were determined in these biospecimens using multi-label immunofluorescence staining and multi-spectral acquisition technology. The clinical roles of TCF-1+PD-1+CD8+T cells were assessed via analyzing our cases and human NSCLC data collected from public databases.
Results
A high frequency of TCF-1+PD-1+CD8+T cells was identified in responders compared with non-responders (p = 0.0024), and the patients with high expression of this cell subset had durable clinical benefit of anti-PD-1 therapy. There were no significant association between the expression of TCF-1+PD-1+CD8+T cells and patients’ age, smoking history, pathologic type, and genetic status. In univariate analysis by the Cox hazard model, high frequency of TCF-1+ PD-1+ CD8+T cells was significantly correlated with patients’ benefit of PD-1 blockade (p = 0.024).
Conclusion
Our study indicated that TCF-1+PD-1+CD8+T cells are associated with the response to PD-1 blockade, and may be a predictor of anti-PD-1 therapy.
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Data availability
The data sets analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
The code was analyzed for bioinformation available from the corresponding author on reasonable request.
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Acknowledgements
We thank Yudong Zhang and Jun Gu (Department of pathology, Shanghai Tongji Hospital, Tongji University School of Medicine) for their kind assistant of pathological experiment.
Funding
This study was supported by the Postdoctoral Science Foundation of China (2020M671233), the Youth Project of National Natural Science Foundation of China (82103412), National Natural Science Foundation of China (81600043, 81800063), Shanghai Natural Science Foundation (16ZR1432100, 19ZR1448500), and Shanghai Health Bureau Key Special Fund for Medicine (20134034).
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XF, SG, XY, and LZ contributed to the conception of the study and manuscript preparation. GW, JH, NW, and PZ contributed to analyze the clinical data. XZ, MC, HZ, TD, and YZ contributed to collect and perform the bioinformation. LZ and YL contributed to the preparation of pathological sections.
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This study was approved by the ethic committee of Tongji Hospital, Tongji University School of Medicine.
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Supplementary file1 Deconvolution analysis of transcriptomes from human NSCLC with different response to PD-1 blockade (GSE145896) (DOCX 22 KB)
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Fang, X., Wu, G., Hua, J. et al. TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer patients. J Cancer Res Clin Oncol 148, 2653–2660 (2022). https://doi.org/10.1007/s00432-021-03845-7
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DOI: https://doi.org/10.1007/s00432-021-03845-7