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Circulating myeloid-derived suppressors cells correlate with clinicopathological characteristics and outcomes undergoing neoadjuvant chemoimmunotherapy in non-small cell lung cancer

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Abstract

Purpose

Myeloid-derived suppressors cells (MDSCs) are heterogeneous immunosuppressive cells, closely related to the development, efficacy and prognosis in various tumors. The relationship between clinicopathological characteristics, efficacy of neoadjuvant chemoimmunotherapy (NCIO) and circulating MDSCs in patients with non-small cell lung cancer (NSCLC) was investigated in this study.

Methods

This study analyzed the clinical data of patients diagnosed at Department of Thoracic Surgery, Beijing Chest Hospital from November 2020 to August 2021. MDSCs and T cells subgroups were measured in fresh peripheral blood mononuclear cells(PBMCs) at baseline. Flow cytometry was used to detect MDSCs and T cells subgroups.

Results

A total of 78 patients with NSCLC and 20 patients with benign nodule underwent direct surgery. 23 patients with NSCLC scheduled to accept NCIO before surgery. NSCLC had elevated levels of total MDSCs, PMN-MDSCs and M-MDSCs compared to patients with benign nodule. MDSCs subgroups were correlated to the pTNM stage in NSCLC patients. The frequency of total MDSCs were moderately positively correlated with regulatory T cells (Tregs)(r = 0.3597, P < 0.01) and negatively correlated with CD4 + T cells(r = 0.2714, P < 0.05). The baseline levels of total MDSCs, PMN-MDSCs and Tregs in pCR patients were significantly decreased than those of non-pCR patients (P < 0.05).

Conclusion

Circulating MDSCs were increased in NSCLC patients. MDSC subgroups were related to pTNM stage in NSCLC patients. Total MDSCs were positively correlated with Tregs levels and negatively correlated with CD4 + T cells in peripheral blood. The level of MDSCs and Tregs in peripheral blood may have potential value in predicting pathological response in NSCLC.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.

    Article  PubMed  Google Scholar 

  2. Scott WJ, Howington J, Feigenberg S, Movsas B, Pisters K, American College of Chest Physicians. Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132(3 Suppl):234S-242S. https://doi.org/10.1378/chest.07-1378.

    Article  PubMed  Google Scholar 

  3. Kang J, Zhang C, Zhong WZ. Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art. Cancer Commun (Lond). 2021;41(4):287–302. https://doi.org/10.1002/cac2.12153.

    Article  Google Scholar 

  4. Melek H, Çetinkaya G, Özer E, et al. Pathological complete response after neoadjuvant/induction treatment: where is its place in the lung cancer staging system?†. Eur J Cardiothorac Surg. 2019;56(3):604–11. https://doi.org/10.1093/ejcts/ezz044.

    Article  PubMed  Google Scholar 

  5. Liu J, Blake SJ, Yong MC, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6(12):1382–99. https://doi.org/10.1158/2159-8290.CD-16-0577.

    Article  CAS  PubMed  Google Scholar 

  6. Talmadge JE, Gabrilovich DI. History of myeloid-derived suppressor cells. Nat Rev Cancer. 2013;13(10):739–52. https://doi.org/10.1038/nrc3581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen L, Xiong L, Hong S, et al. Circulating myeloid-derived suppressor cells facilitate invasion of thyroid cancer cells by repressing miR-486–3p. J Clin Endocrinol Metab. 2020;105(8):dgaa344. https://doi.org/10.1210/clinem/dgaa344.

    Article  PubMed  Google Scholar 

  8. Safarzadeh E, Hashemzadeh S, Duijf PHG, et al. Circulating myeloid-derived suppressor cells: an independent prognostic factor in patients with breast cancer. J Cell Physiol. 2019;234(4):3515–25. https://doi.org/10.1002/jcp.26896.

    Article  CAS  PubMed  Google Scholar 

  9. Ornstein MC, Diaz-Montero CM, Rayman P, et al. Myeloid-derived suppressors cells (MDSC) correlate with clinicopathologic factors and pathologic complete response (pCR) in patients with urothelial carcinoma (UC) undergoing cystectomy. Urol Oncol. 2018;36(9):405–12. https://doi.org/10.1016/j.urolonc.2018.02.018.

    Article  CAS  PubMed  Google Scholar 

  10. Martens A, Wistuba-Hamprecht K, Geukes Foppen M, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res. 2016;22(12):2908–18. https://doi.org/10.1158/1078-0432.CCR-15-2412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pico de Coaña Y, Wolodarski M, van der Haar ÀI, et al. PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates. Oncoimmunology. 2020;9(1):1786888. https://doi.org/10.1080/2162402X.2020.1786888 (Published 2020 Aug 28).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bronte V, Brandau S, Chen SH, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150. https://doi.org/10.1038/ncomms12150 (Published 2016 Jul 6).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yang X, Yin R, Xu L. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;379(9): e14. https://doi.org/10.1056/NEJMc1808251.

    Article  PubMed  Google Scholar 

  14. Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020;21(6):786–95. https://doi.org/10.1016/S1470-2045(20)30140-6.

    Article  CAS  PubMed  Google Scholar 

  15. de Haas N, de Koning C, Spilgies L, de Vries IJ, Hato SV. Improving cancer immunotherapy by targeting the STATe of MDSCs. Oncoimmunology. 2016;5(7):e1196312. https://doi.org/10.1080/2162402X.2016.1196312 (Published 2016 Jun 27).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. OuYang LY, Wu XJ, Ye SB, et al. Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer. J Transl Med. 2015;13(47):1. https://doi.org/10.1186/s12967-015-0410-7 (Published 2015 Feb 1).

    Article  CAS  Google Scholar 

  17. Ma P, Beatty PL, McKolanis J, Brand R, Schoen RE, Finn OJ. Circulating myeloid derived suppressor cells (MDSC) that accumulate in premalignancy share phenotypic and functional characteristics with MDSC in cancer. Front Immunol. 2019;10:1401. https://doi.org/10.3389/fimmu.2019.01401 (Published 2019 Jun 19).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Barrera L, Montes-Servín E, Hernandez-Martinez JM, et al. Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer. Cancer Immunol Immunother. 2018;67(9):1393–406. https://doi.org/10.1007/s00262-018-2196-y.

    Article  CAS  PubMed  Google Scholar 

  19. Chansky K, Detterbeck FC, Nicholson AG, et al. The IASLC lung cancer staging project: external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2017;12(7):1109–21. https://doi.org/10.1016/j.jtho.2017.04.011.

    Article  PubMed  Google Scholar 

  20. Lou F, Sima CS, Rusch VW, Jones DR, Huang J. Differences in patterns of recurrence in early-stage versus locally advanced non-small cell lung cancer. Ann Thorac Surg. 2014;98(5):1755–61. https://doi.org/10.1016/j.athoracsur.2014.05.070.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gentzler RD, Riley DO, Martin LW. Striving toward improved outcomes for surgically resectable non-small cell lung cancer: the promise and challenges of neoadjuvant immunotherapy. Curr Oncol Rep. 2020;22(11):109. https://doi.org/10.1007/s11912-020-00969-w (Published 2020 Aug 15).

    Article  PubMed  Google Scholar 

  22. Leonetti A, Wever B, Mazzaschi G, et al. Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer. Drug Resist Updat. 2019;46: 100644. https://doi.org/10.1016/j.drup.2019.100644.

    Article  PubMed  Google Scholar 

  23. Provencio-Pulla M, Nadal-Alforja E, Cobo M, et al. Neoadjuvant chemo/immunotherapy for the treatment of stages IIIA resectable non-small cell lung cancer (NSCLC): a phase II multicenter exploratory study—NADIM study-SLCG. J Clin Oncol. 2018;36(15_suppl):8521–8521.

    Article  Google Scholar 

  24. Fransen MF, Schoonderwoerd M, Knopf P, et al. Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. JCI Insight. 2018;3(23):e124507. https://doi.org/10.1172/jci.insight.124507 (Published 2018 Dec 6).

    Article  PubMed Central  Google Scholar 

  25. Jones D, Wang Z, Chen IX, et al. Solid stress impairs lymphocyte infiltration into lymph-node metastases. Nat Biomed Eng. 2021;5(12):1426–36. https://doi.org/10.1038/s41551-021-00766-1.

    Article  CAS  PubMed  Google Scholar 

  26. Niu M, Yi M, Li N, Luo S, Wu K. Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC. Exp Hematol Oncol. 2021;10(1):18. https://doi.org/10.1186/s40164-021-00211-8 (Published 2021 Mar 2).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kurtulus S, Madi A, Escobar G, et al. Checkpoint blockade immunotherapy induces dynamic changes in PD-1-CD8+ tumor-infiltrating T cells. Immunity. 2019;50(1):181-194.e6. https://doi.org/10.1016/j.immuni.2018.11.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yost KE, Satpathy AT, Wells DK, et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med. 2019;25(8):1251–9. https://doi.org/10.1038/s41591-019-0522-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–74. https://doi.org/10.1038/nri2506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Weber R, Fleming V, Hu X, et al. Myeloid-derived suppressor cells hinder the anti-cancer activity of immune checkpoint inhibitors. Front Immunol. 2018;9:1310. https://doi.org/10.3389/fimmu.2018.01310 (Published 2018 Jun 11).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kim HR, Park SM, Seo SU, et al. The ratio of peripheral regulatory T cells to Lox-1+ polymorphonuclear myeloid-derived suppressor cells predicts the early response to anti-PD-1 therapy in patients with non-small cell lung cancer. Am J Respir Crit Care Med. 2019;199(2):243–6. https://doi.org/10.1164/rccm.201808-1502LE.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gambichler T, Schröter U, Höxtermann S, Susok L, Stockfleth E, Becker JC. Decline of programmed death-1-positive circulating T regulatory cells predicts more favourable clinical outcome of patients with melanoma under immune checkpoint blockade. Br J Dermatol. 2020;182(5):1214–20. https://doi.org/10.1111/bjd.18379.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. No. 2 Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China

    T. Wen, C. Su, X. Cheng, Y. Wang, T. Ma, Z. Bai & Z. Liu

  2. Department of Central Laboratory, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China

    H. Zhang

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Correspondence to Z. Liu.

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All authors in this study declare no competing interests.

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This research was approved by the Institutional Ethics Committee in Beijing chest hospital and was carried out according to the Ethical Principles of the Declaration of Helsinki.

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All patients provided written informed consent before study inclusion.

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Wen, T., Su, C., Cheng, X. et al. Circulating myeloid-derived suppressors cells correlate with clinicopathological characteristics and outcomes undergoing neoadjuvant chemoimmunotherapy in non-small cell lung cancer. Clin Transl Oncol 24, 1184–1194 (2022). https://doi.org/10.1007/s12094-021-02765-9

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