Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

Ahead of print

doi: 10.17219/acem/159242

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Hou Z, Zhao L, Zou L, Li B. The prognostic value of tumor-infiltrating lymphocytes in non-small cell lung cancer patients who received neoadjuvant chemotherapy followed by surgery [published online as ahead of print on March 7, 2023]. Adv Clin Exp Med. 2023. doi:10.17219/acem/159242

The prognostic value of tumor-infiltrating lymphocytes in non-small cell lung cancer patients who received neoadjuvant chemotherapy followed by surgery

Zexin Hou1,A,C,D, Lili Zhao1,E,F, Lingjun Zou1,B,C, Benlan Li2,B,C

1 Department of Oncology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, China

2 Department of Pathology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, China

Abstract

Background. The relationship between tumor-infiltrating lymphocyte (TIL) levels and the prognosis of patients with non-small cell lung cancer (NSCLC) who receive neoadjuvant chemotherapy followed by surgery is a problem that requires more research.
Objectives. To evaluate the prognostic value of TIL levels in patients with NSCLC who received neoadjuvant chemotherapy followed by surgery.
Material and Methods. Patients with NSCLC who received neoadjuvant chemotherapy followed by surgery in our hospital from December 2014 to December 2020 were selected for a retrospective analysis. Sections were stained with hematoxylin and eosin (H&E) to evaluate TIL levels in surgically-resected tumor tissues. Patients were divided into TIL(low-level infiltration) and TIL+ (mediumto high-level infiltration) groups according to the recommended TIL evaluation criteria. Univariate (Kaplan–Meier) and multivariate (Cox) survival analyses were used to analyze the impact of clinicopathological features and TIL levels on prognosis.
Results. The study involved 137 patients, including 45 who were TILand 92 who were TIL+. The median overall survival (OS) and disease-free survival (DFS) of the TIL+ group were higher than those of the TILgroup. The univariate analysis showed that smoking, clinical and pathological stages, and TIL levels, were the factors influencing OS and DFS. The multivariate analysis showed that smoking (OS, hazard ratio (HR): 1.881, 95% confidence interval (95% CI): 1.135–3.115, p = 0.014; DFS, HR: 1.820, 95% CI: 1.181–2.804, p = 0.007) and clinical stage III (DFS, HR: 2.316, 95% CI: 1.350–3.972, p = 0.002) were adverse factors affecting the prognosis of patients with NSCLC who received neoadjuvant chemotherapy followed by surgery. At the same time, TIL+ status was an independent factor for a good prognosis in OS (HR: 0.547, 95% CI: 0.335–0.894, p = 0.016) and DFS (HR: 0.445, 95% CI: 0.284–0.698, p = 0.001).
Conclusion. Medium to high levels of TILs were associated with a good prognosis in NSCLC patients who received neoadjuvant chemotherapy followed by surgery. The levels of TILs are of prognostic value in this population of patients.

Key words

non-small cell lung cancer, overall survival, neoadjuvant chemotherapy, disease-free survival, tumor-infiltrating lymphocyte

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References (28)

  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
  2. Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94(8):1623–1640. doi:10.1016/j.mayocp.2019.01.013
  3. Kocher F, Hilbe W, Seeber A, et al. Longitudinal analysis of 2293 NSCLC patients: A comprehensive study from the TYROL registry. Lung Cancer. 2015;87(2):193–200. doi:10.1016/j.lungcan.2014.12.006
  4. Sinn K, Mosleh B, Steindl A, et al. Neoadjuvant chemoradiotherapy is superior to chemotherapy alone in surgically treated stage III/N2 non-small-cell lung cancer: A retrospective single-center cohort study. ESMO Open. 2022;7(2):100466. doi:10.1016/j.esmoop.2022.100466
  5. Montemuiño S, de Dios NR, Martín M, et al. High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC: A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society). Rep Pract Oncol Radiother. 2020;25(3):447–455. doi:10.1016/j.rpor.2020.03.006
  6. Darling GE, Li F, Patsios D, et al. Neoadjuvant chemoradiation and surgery improves survival outcomes compared with definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung cancer. Eur J Cardiothorac Surg. 2015;48(5):684–690. doi:10.1093/ejcts/ezu504
  7. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–264. doi:10.1038/nrc3239
  8. Horne ZD, Jack R, Gray ZT, et al. Increased levels of tumor-infiltrating lymphocytes are associated with improved recurrence-free survival in stage 1A non-small-cell lung cancer. J Surg Res. 2011;171(1):1–5. doi:10.1016/j.jss.2011.03.068
  9. Ku BM, Kim Y, Lee KY, et al. Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non‐small cell lung cancer. Eur J Immunol. 2021;51(4):956–964. doi:10.1002/eji.202048966
  10. Caparica R, Bruzzone M, Agostinetto E, et al. Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis. Breast. 2021;59:183–192. doi:10.1016/j.breast.2021.07.007
  11. Casanova JM, Almeida JS, Reith JD, et al. Tumor-infiltrating lymphocytes and cancer markers in osteosarcoma: Influence on patient survival. Cancers. 2021;13(23):6075. doi:10.3390/cancers13236075
  12. Gataa I, Mezquita L, Rossoni C, et al. Tumour-infiltrating lymphocyte density is associated with favourable outcome in patients with advanced non-small cell lung cancer treated with immunotherapy. Eur J Cancer. 2021;145:221–229. doi:10.1016/j.ejca.2020.10.017
  13. Kumar A, Kumar S, Gilja S, et al. Reconsidering the American Joint Committee on Cancer Eighth Edition TNM Staging Manual Classifications for T2b and T3 NSCLC. J Thorac Oncol. 2021;16(10):1672–1683. doi:10.1016/j.jtho.2021.06.016
  14. Zhao L, Zhang L, Gong F, Xu J. Thoracoscopic radical resection in the treatment of NSCLC patients (stage IIIA) after neoadjuvant chemotherapy. J BUON. 2021;26(2):313–319. PMID:34076974.
  15. Yu WD, Sun G, Li J, Xu J, Wang X. Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy. Cancer Lett. 2019;452:66–70. doi:10.1016/j.canlet.2019.02.048
  16. Xie QK, He WZ, Hu WM, et al. Tumor-infiltrating lymphocyte as a prognostic biomarker in stage IV colorectal cancer should take into account the metastatic status and operation modality. Cancer Manag Res. 2018;10:1365–1375. doi:10.2147/CMAR.S162147
  17. Feng W, Li Y, Shen L, et al. Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer. Oncotarget. 2016;7(6):7227–7240. doi:10.18632/oncotarget.6979
  18. Gataa I, Mezquita L, Rossoni C, et al. Tumour-infiltrating lymphocyte density is associated with favourable outcome in patients with advanced non-small cell lung cancer treated with immunotherapy. Eur J Cancer. 2021;145:221–229. doi:10.1016/j.ejca.2020.10.017
  19. Lee TK, Horner RD, Silverman JF, Chen YH, Jenny C, Scarantino CW. Morphometric and morphologic evaluations in stage III non-small cell lung cancers: Prognostic significance of quantitative assessment of infiltrating lymphoid cells. Cancer. 1989;63(2):309–316. doi:10.1002/1097-0142(19890115)63:2<309::aid-cncr2820630218>3.0.co;2-n
  20. Rakaee M, Kilvaer TK, Dalen SM, et al. Evaluation of tumor-infiltrating lymphocytes using routine H&E slides predicts patient survival in resected non-small cell lung cancer. Hum Pathol. 2018;79:188–198. doi:10.1016/j.humpath.2018.05.017
  21. Devarakonda S, Rotolo F, Tsao MS, et al. Tumor mutation burden as a biomarker in resected non–small-cell lung cancer. J Clin Oncol. 2018;36(30):2995–3006. doi:10.1200/JCO.2018.78.1963
  22. Wang WC, Zhang ZQ, Li PP, et al. Anti-tumor activity and mechanism of oligoclonal hepatocellular carcinoma tumor-infiltrating lymphocytes in vivo and in vitro. Cancer Biol Ther. 2019;20(9):1187–1194. doi:10.1080/15384047.2019.1599663
  23. Cullen SP, Martin SJ. Fas and TRAIL ‘death receptors’ as initiators of inflammation: Implications for cancer. Semin Cell Dev Biol. 2015;39:26–34. doi:10.1016/j.semcdb.2015.01.012
  24. Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: Function, dysfunction and human pathology. Nat Rev Immunol. 2015;15(6):388–400. doi:10.1038/nri3839
  25. Trojan A, Urosevic M, Dummer R, Giger R, Weder W, Stahel RA. Immune activation status of CD8+ T cells infiltrating non-small cell lung cancer. Lung Cancer. 2004;44(2):143–147. doi:10.1016/j.lungcan.2003.11.004
  26. Zhuang X, Xia X, Wang C, et al. A high number of CD8+ T cells infiltrated in NSCLC tissues is associated with a favorable prognosis. Appl Immunohistochem Mol Morphol. 2010;18(1):24–28. doi:10.1097/PAI.0b013e3181b6a741
  27. Steuer CE, Jegede OA, Dahlberg SE, et al. Smoking behavior in patients with early-stage NSCLC: A report from ECOG-ACRIN 1505 Trial. J Thorac Oncol. 2021;16(6):960–967. doi:10.1016/j.jtho.2020.12.017
  28. Fujiyoshi K, Chen Y, Haruki K, et al. Smoking status at diagnosis and colorectal cancer prognosis according to tumor lymphocytic reaction. JNCI Cancer Spectr. 2020;4(5):pkaa040. doi:10.1093/jncics/pkaa040
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