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Discover Oncology
Published in: Discover Oncology 1/2023

Open Access 01-12-2023 | NSCLC | Research

Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC

Authors: Ling Yi, Xiaojue Wang, Siyun Fu, Zhuohong Yan, Tianyu Ma, Siqi Li, Panjian Wei, Hongtao Zhang, Jinghui Wang

Published in: Discover Oncology | Issue 1/2023

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Abstract

In this study, we explored the dynamic changes in blood sPD-L1 and its clinical value during anti-PD-1 immunotherapy in non-small cell lung cancer (NSCLC) patients. First, we established a sandwich ELISA for functional sPD-L1 that can bind to PD-1 and has biological functions. By monitoring functional sPD-L1 in 39 NSCLC patients treated with anti-PD-1 antibodies, we found a positive correlation between baseline sPD-L1 and tissue PD-L1 (P = 0.0376, r = 0.3581), with patients with lymph node metastasis having higher sPD-L1 levels (P = 0.0037) than those without lymph node metastasis. Although baseline functional sPD-L1 and PFS did not correlate significantly in this study, changes in sPD-L1 in patients with different clinical responses showed different trends. Blood sPD-L1 increased in 93% of patients after two cycles of anti-PD-1 treatment (P = 0.0054); sPD-L1 in nonresponsive patients continued to increase (P = 0.0181), but sPD-L1 started to decline in responsive patients. Blood IL-8 levels were associated with tumor load, and when combined with IL-8, the evaluation accuracy of sPD-L1 improved to 86.4%. This study preliminarily shows that the combination of sPD-L1 and IL-8 is a convenient and effective method for monitoring and evaluating the effectiveness of anti-PD-1 immunotherapy in NSCLC patients.
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Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92–8.PubMedCrossRef
3.
Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311:1998–2006.PubMedPubMedCentralCrossRef
4.
5.
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefifitinib or carboplatin- paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.PubMedCrossRef
6.
Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77.PubMedCrossRef
7.
Meng X, Liu Y, Zhang J, Teng F, Xing L, Yu J. PD-1/PD-L1 checkpoint blockades in non-small cell lung cancer: new development and challenges. Cancer Lett. 2017;405:29–37.PubMedCrossRef
8.
Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50(12):1–11.PubMedCrossRef
9.
10.
Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, et al. Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin ncol. 2015;33:2004–12.CrossRef
11.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Overall survival with ombined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:345–56.CrossRef
12.
Gong B, Kiyotani K, Sakata S, Nagano S, Kumehara S, Baba S, et al. Secreted PD-L1 variants mediate resistance to PD-L1 blockade therapy in non–small cell lung cancer. J Exp Med. 2019;216(4):982.PubMedPubMedCentralCrossRef
13.
Shi L, Chen S, Yang L, Li Y. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol. 2013;6(1):74.PubMedPubMedCentralCrossRef
14.
15.
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol. 2016;2(1):46–54.PubMedPubMedCentralCrossRef
16.
Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20:5064–74.PubMedPubMedCentralCrossRef
17.
Rasmussen JH, Lelkaitis G, Håkansson K, Vogelius IR, Johannesen HH, Fischer BM, Bentzen SM, Specht L, Kristensen CA, von Buchwald C, Wessel I, Friborg J. Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma. Br J Cancer. 2019;120(10):1003–6.PubMedPubMedCentralCrossRef
18.
Takeuchi M, Doi T, Obayashi K, Hirai A, Yoneda K, Tanaka F, Iwai Y. Soluble PD-L1 with PD-1-binding capacity exists in the plasma of patients with non-small celllung cancer. Immunol Lett. 2018;196:155–60.PubMedCrossRef
19.
Finkelmeier F, Canli O, Tal A, Pleli T, Trojan J, Schmidt M, et al. High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis. Eur J Cancer. 2016;59:152–9.PubMedCrossRef
20.
Okuma Y, Hosomi Y, Nakahara Y, Watanabe K, Sagawa Y, Homma S. High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer. Lung Cancer. 2017;104:1–6.PubMedCrossRef
21.
Chang B, Huang T, Wei H, Shen L, Zhu D, He W, et al. The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma. Cancer Immunol Immunother. 2019;68:353–63.PubMedCrossRef
22.
Shigemori T, Toiyama Y, Okugawa Y, Yamamoto A, Yin C, Narumi A, et al. Soluble PD-L1 expression in circulation as a predictive marker for recurrence and prognosis in gastric cancer: direct comparison of the clinical burden between tissue and serum PD-L1 expression. Ann Surg Oncol. 2019;26:876–83.PubMedCrossRef
23.
Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, et al. Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade. Cancer Immunol Res. 2017;5:480–92.PubMedPubMedCentralCrossRef
24.
Frigola X, Inman BA, Lohse CM, Krco CJ, Cheville JC, Thompson RH, et al. Identifification of a soluble form of B7–H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clin Cancer Res. 2011;17:1915–23.PubMedPubMedCentralCrossRef
25.
Ugurel S, Schadendorf D, Horny K, Sucker A, Schramm S, Utikal J, et al. Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma. Ann Oncol. 2020;31(1):144–52.PubMedCrossRef
26.
Okuma Y, Wakui H, Utsumi H, Sagawa Y, Hosomi Y, Kuwano K, et al. Soluble programmed cell death ligand 1 as a novel biomarker for nivolumab therapy for non-small-cell lung cancer. Clin Lung Cancer. 2018;19(5):410–7.PubMedCrossRef
27.
Bonomi M, Ahmed T, Addo S, Kooshki M, Palmieri D, Levine BJ, et al. Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: an interim analysis. Oncol Lett. 2019;17(1):1349–56.PubMed
28.
Abu Hejleh T, Furqan M, Ballas Z, Clamon G. The clinical significance of soluble PD-1 and PD-L1 in lung cancer. Crit Rev Oncol Hematol. 2019;143:148–52.PubMedCrossRef
29.
Kim HJ, Park S, Kim K-J, Seong J. Clinical signifificance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2018;129(1):130–5.CrossRef
30.
Ha H, Bang J-H, Nam A-R, Park J-E, Jin MH, Bang Y-J, et al. Dynamics of soluble programmed death-ligand 1 (sPDL1) during chemotherapy and its prognostic implications in cancer patients: biomarker development in immuno-oncology. Cancer Res Treat. 2019;51(2):832–40.PubMedCrossRef
31.
Fukuda T, Kamai T, Masuda A, Nukui A, Abe H, Arai K, Yoshida K. Higher preoperative serum levels of PD-L1 and B7–H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF-targeted therapy and unfavorable prognosis of renal cell carcinoma. Cancer Med. 2016;5(8):1810–20.PubMedPubMedCentralCrossRef
32.
Park W, Bang J-H, Nam A-R, Park JE, Kim MH, Oh KS, et al. Prognostic value of serum soluble programmed death-ligand 1 (sPDL1) and dynamics during chemotherapy in advanced gastric cancer patients. J Clin Oncol. 2019;37(15_suppl):4034.CrossRef
33.
Murakami S, Shibaki R, Matsumoto Y, Yoshida T, Goto Y, Kanda S, et al. Association between serum level soluble programmed cell death ligand 1 and prognosis in patients with non-small cell lung cancer treated with anti-PD-1 antibody. Thorac Cancer. 2020;11(12):3585–95.PubMedPubMedCentralCrossRef
34.
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;148:1–11.PubMedCrossRef
35.
Buder-Bakhaya K, Hassel JC. Biomarkers for clinical benefit of immune checkpoint inhibitor treatment-a review from the melanoma perspective and beyond. Front Immunol. 2018;9:1474.PubMedPubMedCentralCrossRef
36.
Han B, Dong L, Zhou J, Yang Y, Guo J, Xuan Q, et al. The clinical implication of soluble PD-L1 (sPD-L1) in patients with breast cancer and its biological function in regulating the function of T lymphocyte. Cancer Immunol Immunother. 2021;70(10):2893–909.PubMedPubMedCentralCrossRef
37.
Takahashi N, Iwasa S, Sasaki Y, Shoji H, Honma Y, Takashima A, et al. Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer. J Cancer Res Clin Oncol. 2016;142(8):1727–38.PubMedCrossRef
38.
Ando K, Hamada K, Watanabe M, Ohkuma R, Shida M, Onoue R,et al. Plasma levels of soluble PD-L1 correlate with tumor regression in patients with lung and gastric cancer treated with immune checkpoint inhibitors. Anticancer Res. 2019;39(9):5195–201.PubMedCrossRef
39.
Mahoney KM, Ross-Macdonald P, Yuan L, Song L, Veras E, Wind-Rotolo M, et al. Soluble PD-L1 as an early marker of progressive disease on nivolumab. J Immunother Cancer. 2022;10(2):e003527.PubMedPubMedCentralCrossRef
40.
Shuping L, Xiaojue W, Bin Y, Helin W, Zhuohong Y, Ling Y, et al. Construcion and expression of chimeric antigen receptors targetingepidermal growth factor receptor(EGFR) and programmed cell death ligand-1(PD-L1). Chin J Microbiol Immunol. 2020;40(3):198–205.
41.
Li S, Yi L, Wei X, Zhang J, Wang X, Jiang C, et al. Soluble programmed cell death-ligand 1 as a new potential biomarker associated with acute coronary syndrome. Front Cardiovasc Med. 2022;2(9):971414.CrossRef
42.
Castello A, Rossi S, Toschi L, Mansi L, Lopci E. Soluble PD-L1 in NSCLC patients treated with checkpoint inhibitors and its correlation with metabolic parameters. Cancers. 2020;12(6):1373.PubMedPubMedCentralCrossRef
43.
Rossille D, Gressier M, Damotte D, Maucort-Boulch D, Pangault C, Semana G, et al. High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial. Leukemia. 2014;28(12):2367–75.PubMedCrossRef
44.
Kruger S, Legenstein ML, Rösgen V, Haas M, Modest DP, Westphalen CB, et al. Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer. Oncoimmunology. 2017;6(5):e1310358.PubMedPubMedCentralCrossRef
45.
Costantini A, Julie C, Dumenil C, Hélias-Rodzewicz Z, Tisserand J, Dumoulin J, et al. Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab. Oncoimmunology. 2018;7(8):e1452581.PubMedPubMedCentralCrossRef
46.
Sanmamed MF, Perez-Gracia JL, Schalper KA, Fusco JP, Gonzalez A, Rodriguez-Ruiz ME, Oñate C, Perez G, et al. Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients. Ann Oncol. 2017;28(8):1988–95.PubMedPubMedCentralCrossRef
47.
Sanmamed MF, Carranza-Rua O, Alfaro C, Oñate C, Martín-Algarra S, Perez G, et al. Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins. Clin Cancer Res. 2014;20(22):5697–707.PubMedCrossRef
48.
Juliá EP, Mandó P, Rizzo MM, Cueto GR, Tsou F, Luca R, et al. Peripheral changes in immune cell populations and soluble mediators after anti-PD-1 therapy in non-small cell lung cancer and renal cell carcinoma patients. Cancer Immunol Immunother. 2019;68(10):1585–96.PubMedCrossRef
49.
Daassi D, Mahoney KM, Freeman GJ. The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 2020;20(4):209–15.PubMedCrossRef
Metadata
Title
Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC
Authors
Ling Yi
Xiaojue Wang
Siyun Fu
Zhuohong Yan
Tianyu Ma
Siqi Li
Panjian Wei
Hongtao Zhang
Jinghui Wang
Publication date
01-12-2023
Publisher
Springer US
Keywords
NSCLC
NSCLC
Published in
Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-023-00641-2

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