Predictive Value of the Lung Immune Prognostic Index for Immune Checkpoint Inhibitor Therapy Outcomes in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Abstract
Non-Small Cell Lung Cancer (NSCLC) patients undergoing Immune Checkpoint Inhibitors (ICIs) therapy exhibit diverse clinical outcomes. The Lung Immune Prognostic Index (LIPI) may emerge as a potential prognostic marker. This study systematically reviews and meta-analyzes the prognostic value of LIPI in predicting the clinical efficacy of ICIs therapy for NSCLC patients. A thorough literature review was performed using the Cochrane Library, Web of Science, PubMed, and Embase, following PRISMA guidelines. Studies assessing LIPI’s predictive value in NSCLC patients treated with ICIs were included. Effect sizes were aggregated utilizing a fixed-effects model. The studies featured in the review were appraised using the Newcastle-Ottawa Scale for quality assessment. Eight studies were incorporated into the meta-analysis, encompassing various treatment lines and ICIs. No substantial heterogeneity was detected across the studies. The meta-analysis revealed that the low-risk group exhibited significantly extended overall survival (OS) (HR=3.18, 95%CI: 2.78~3.59 and progression-free survival (PFS) (HR=1.60, 95%CI: 1.4~61.74, underscoring the predictive significance of LIPI for NSCLC patients treated with ICI therapy. No significant publication bias was detected. LIPI demonstrates potential as a prognostic marker for NSCLC patients receiving ICI therapy, contributing to the development of therapeutic strategies. Further prospective researches are required to investigate its relationship with factors such as tumor mutational burden, PD-L1 and PD-1.
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20. Chen Q, Yang LX, Li XD, Yin D, Shi SM, Chen EB, et al. The elevated preoperative neutrophil-to-lymphocyte ratio predicts poor prognosis in intrahepatic cholangiocarcinoma patients undergoing hepatectomy. Tumour Biol 2015;36(7):5283-9.
21. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-44.
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24. Mezquita L, Preeshagul I, Auclin E. Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics. Eur J Cancer. 2021;151(8):211-20.
25. Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016;16(7):431-46.
26. Colloca GA, Venturino A, Guarneri D. Second-generation inflammation-related scores are more effective than systemic inflammation ratios in predicting prognosis of patients with unresectable or metastatic pancreatic cancer receiving cytotoxic chemotherapy. Med Oncol. 2018;35(12):158.
27. Colloca GA, Venturino A, Guarneri D. Retrospective analysis by site of primary tumor of patients with unresectable locally-advanced or metastatic pancreatic adenocarcinoma receiving chemotherapy. Clin Exp Metastas. 2019;36(6): 519-25.
28. Faget J, Groeneveld S, Boivin G, et al. Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer. Cell Rep. 2017;21(11):3190-3204.
29. Chen XF, Qian J, Pei D. Prognostic value of perioperative leukocyte count in resectable gastric cancer. World J Gastroentero. 2016;22(9):2818-27.
30. Heppt MV, Heinzerling L, Kähler KC, Forschner A, Kirchberger MC, Loquai C, et al. Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer. 2017;82(14):56-65.
31. Schaaf MB, Garg AD, Agostinis P. Defining the role of the tumor vasculature in antitumor immunity and immunotherapy. Cell Death Dis. 2018;9(2):115.
32. Missiaen R, Mazzone M, Bergers G. The reciprocal function and regulation of tumor vessels and immune cells offers new therapeutic opportunities in cancer. Semin Cancer Biol. 2018;52(Pt 2):107-16.
2. Song R, Liu F, Ping Y, Zhang Y, Wang L. Potential non-invasive biomarkers in tumor immune checkpoint inhibitor therapy: response and prognosis prediction. Biomark Res. 2023;11(1):57.
3. Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, et al. Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non-Small-Cell Lung Cancer. J Clin Oncol 2017;35(34):3867-76.
4. Zhang S, Bai X, Shan F. The progress and confusion of anti-PD1/PD-L1 immunotherapy for patients with advanced non-small cell lung cancer. Int Immunopharmacol. 2020; 80:106247.
5. Yang T, Hao L, Yang X, Luo C, Wang G, Lin Cai C, et al. Prognostic value of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with non-small cell lung cancer receiving immune checkpoint inhibitors: a meta-analysis. Bmj Open. 2021;11(9):e049123.
6. Zhang N, Jiang J, Tang S, Sun G. Predictive value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis. Int Immunopharmacol. 2020;85:106677.
7. Hopkins AM, Kichenadasse G, McKinnon RA, Rowland A, Sorich MJ. Baseline tumor size and survival outcomes in lung cancer patients treated with immune checkpoint inhibitors. Semin Oncol. 2019;46(4-5): 380-4.
8. Minami S, Ihara S, Komuta K. Pretreatment Lung Immune Prognostic Index Is a Prognostic Marker of Chemotherapy and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor. World J Oncol. 2019;10(1):35-45.
9. Benitez JC, Recondo G, Rassy E, Mezquita L. The LIPI score and inflammatory biomarkers for selection of patients with solid tumors treated with checkpoint inhibitors. Q J Nucl Med Mol Im. 2020;64(2):162-74.
10. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj-Brit Med J. 2021;372: n71.
11. Scheidt S, Vavken P, Jacobs C, Koob S, Cucchi D, Kaup E, et al. Systematic Reviews and Meta-analyses. Z Orthop Unfallchir. 2019;157(4):392-9.
12. Hopkins AM, Kichenadasse G, Abuhelwa AY, McKinnon RA, Rowland A, Sorich MJ. Value of the Lung Immune Prognostic Index in Patients with Non-Small Cell Lung Cancer Initiating First-Line Atezolizumab Combination Therapy: Subgroup Analysis of the IMPOWER150 Trial. Cancers 2021;13(5).
13. Hopkins AM, Wagner J, Kichenadasse G, Modi N, Rowland A, Sorich MJ. Patient-reported outcomes as a prognostic marker of survival in patients with advanced nonsmall cell lung cancer treated with immunotherapy. Int J Cancer. 2020;147(11):3085-9.
14. Kazandjian D, Gong Y, Keegan P, Pazdur R, Blumenthal GM. Prognostic Value of the Lung Immune Prognostic Index for Patients Treated for Metastatic Non-Small Cell Lung Cancer. Jama Oncol. 2019; 5(10):1481-5.
15. Mazzaschi G, Minari R, Zecca A, Cavazzoni A, Ferri V, Mori C, et al. Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients. Lung Cancer. 2020;148(5):1-11.
16. Mezquita L, Auclin E, Ferrara R, Charrier M, Remon J, Planchard D, et al. Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer. Jama Oncol. 2018;4(3):351-7.
17. Ruiz-Banobre J, Areses-Manrique MC, Mosquera-Martinez J. Evaluation of the lung immune prognostic index in advanced non-small cell lung cancer patients under nivolumab monotherapy. Transl Lung Cancer R. 2019;8(6):1078-85.
18. Sorich MJ, Rowland A, Karapetis CS, Hopkins AM. Evaluation of the Lung Immune Prognostic Index for Prediction of Survival and Response in Patients Treated With Atezolizumab for NSCLC: Pooled Analysis of Clinical Trials. J Thorac Oncol. 2019;14(8):1440-6.
19. Wang W, Huang Z, Yu Z, et al. Prognostic Value of the Lung Immune Prognostic Index May Differ in Patients Treated With Immune Checkpoint Inhibitor Monotherapy or Combined With Chemotherapy for Non-small Cell Lung Cancer. Front Oncol. 2020;10(4):572853.
20. Chen Q, Yang LX, Li XD, Yin D, Shi SM, Chen EB, et al. The elevated preoperative neutrophil-to-lymphocyte ratio predicts poor prognosis in intrahepatic cholangiocarcinoma patients undergoing hepatectomy. Tumour Biol 2015;36(7):5283-9.
21. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-44.
22. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144(5):646-74.
23. Cho Y, Kim JW, Yoon HI, Lee CG, Keum KC, Lee IJ. The Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Head and Neck Cancer Patients Treated with Radiotherapy. J Clin Med. 2018;7(12).
24. Mezquita L, Preeshagul I, Auclin E. Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics. Eur J Cancer. 2021;151(8):211-20.
25. Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016;16(7):431-46.
26. Colloca GA, Venturino A, Guarneri D. Second-generation inflammation-related scores are more effective than systemic inflammation ratios in predicting prognosis of patients with unresectable or metastatic pancreatic cancer receiving cytotoxic chemotherapy. Med Oncol. 2018;35(12):158.
27. Colloca GA, Venturino A, Guarneri D. Retrospective analysis by site of primary tumor of patients with unresectable locally-advanced or metastatic pancreatic adenocarcinoma receiving chemotherapy. Clin Exp Metastas. 2019;36(6): 519-25.
28. Faget J, Groeneveld S, Boivin G, et al. Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer. Cell Rep. 2017;21(11):3190-3204.
29. Chen XF, Qian J, Pei D. Prognostic value of perioperative leukocyte count in resectable gastric cancer. World J Gastroentero. 2016;22(9):2818-27.
30. Heppt MV, Heinzerling L, Kähler KC, Forschner A, Kirchberger MC, Loquai C, et al. Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer. 2017;82(14):56-65.
31. Schaaf MB, Garg AD, Agostinis P. Defining the role of the tumor vasculature in antitumor immunity and immunotherapy. Cell Death Dis. 2018;9(2):115.
32. Missiaen R, Mazzone M, Bergers G. The reciprocal function and regulation of tumor vessels and immune cells offers new therapeutic opportunities in cancer. Semin Cancer Biol. 2018;52(Pt 2):107-16.
| Files | ||
| Issue | Vol 24 No 2 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Immune checkpoint inhibitors Lung immune prognostic index Meta-analysis Non-small cell lung cancer | ||
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How to Cite
1.
Lu W, Su J. Predictive Value of the Lung Immune Prognostic Index for Immune Checkpoint Inhibitor Therapy Outcomes in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Iran J Allergy Asthma Immunol. 2025;24(2):132-142.
