Immunophenotyping of peripheral blood in NSCLC patients discriminates responders to immune checkpoint inhibitors.
Biomarkers
Checkpoint inhibitors
Immunotherapy
NSCLC
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
21 Feb 2024
21 Feb 2024
Historique:
received:
30
11
2023
accepted:
19
01
2024
medline:
22
2
2024
pubmed:
22
2
2024
entrez:
22
2
2024
Statut:
epublish
Résumé
Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy. In this prospective observational cohort study, we investigated the predictive role of erythrocytes, thrombocytes, innate and adaptive immune cells, complement proteins (C3, C4), and cytokines from peripheral blood of 224 patients with stage III/IV NSCLC treated with ICI alone (pembrolizumab, nivolumab, and atezolizumab) or in combination (nivolumab + ipilimumab) with chemotherapy. These values were analyzed for associations with the response to the treatment and survival endpoints. Higher baseline Tregs, MPV, hemoglobin, and lower monocyte levels were associated with favorable PFS and OS. Moreover, increased baseline basophils and lower levels of C3 predicted significantly improved PFS. The levels of the baseline immature granulocytes, C3, and monocytes were significantly associated with the occurrence of partial regression at the first restaging. Multiple studied parameters (n = 9) were related to PFS benefit at the time of first restaging as compared to baseline values. In addition, PFS nonbenefit group showed a decrease in lymphocyte count after three months of therapy. The OS benefit was associated with higher levels of lymphocytes, erythrocytes, hemoglobin, MCV, and MPV, and a lower value of NLR after three months of treatment. Our work suggests that parameters from peripheral venous blood may be potential biomarkers in NSCLC patients on ICI. The baseline values of Tregs, C3, monocytes, and MPV are especially recommended for further investigation.
Identifiants
pubmed: 38383923
doi: 10.1007/s00432-024-05628-2
pii: 10.1007/s00432-024-05628-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
99Subventions
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NV19-03-00179
Informations de copyright
© 2024. The Author(s).
Références
An HJ, Chon HJ, Kim C (2021) Peripheral blood-based biomarkers for immune checkpoint inhibitors. Int J Mol Sci 22(17):9414. https://doi.org/10.3390/IJMS22179414
doi: 10.3390/IJMS22179414
pubmed: 34502325
pmcid: 8430528
Ayers KL, Ma M, Debussche G et al (2021) A composite biomarker of neutrophil-lymphocyte ratio and hemoglobin level correlates with clinical response to PD-1 and PD-L1 inhibitors in advanced non-small cell lung cancers. BMC Cancer 21(1):441. https://doi.org/10.1186/s12885-021-08194-9
doi: 10.1186/s12885-021-08194-9
pubmed: 33882890
pmcid: 8059160
Bagley SJ, Kothari S, Aggarwal C et al (2017) Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer 106:1–7. https://doi.org/10.1016/J.LUNGCAN.2017.01.013
doi: 10.1016/J.LUNGCAN.2017.01.013
pubmed: 28285682
Caliman E, Fancelli S, Ottanelli C et al (2022) Absolute eosinophil count predicts clinical outcomes and toxicity in non-small cell lung cancer patients treated with immunotherapy. Cancer Treat Res Commun 32:100603. https://doi.org/10.1016/J.CTARC.2022.100603
doi: 10.1016/J.CTARC.2022.100603
pubmed: 35792426
Chauhan J, Stavraka C, Grandits M et al (2022) Clinical and translational significance of basophils in patients with cancer. Cells 11(3):438. https://doi.org/10.3390/CELLS11030438/S1
doi: 10.3390/CELLS11030438/S1
pubmed: 35159247
pmcid: 8833920
Chocarro L, Blanco E, Zuazo M et al (2021) Understanding LAG-3 signaling. Int J Mol Sci 22(10):5282. https://doi.org/10.3390/IJMS22105282
doi: 10.3390/IJMS22105282
pubmed: 34067904
pmcid: 8156499
Derman BA, Macklis JN, Azeem MS et al (2017) Relationships between longitudinal neutrophil to lymphocyte ratios, body weight changes, and overall survival in patients with non-small cell lung cancer. BMC Cancer 17(1):141. https://doi.org/10.1186/S12885-017-3122-Y
doi: 10.1186/S12885-017-3122-Y
pubmed: 28209123
pmcid: 5312530
Ettinger DS, Wood DE, Aisner DL et al (2023) NCCN guidelines Version 5.2023 non-small cell lung cancer continue NCCN guidelines panel disclosures. Published online 2023. Accessed October 2, 2023
Giommoni E, Giorgione R, Paderi A et al (2021) Eosinophil count as predictive biomarker of immune-related adverse events (irAEs) in immune checkpoint inhibitors (ICIs) therapies in oncological patients. Immuno 1(3):253–263. https://doi.org/10.3390/immuno1030017
doi: 10.3390/immuno1030017
Grisaru-Tal S, Rothenberg ME, Munitz A (2022) Eosinophil–lymphocyte interactions in the tumor microenvironment and cancer immunotherapy. Nat Immunol 23(9):1309–1316. https://doi.org/10.1038/s41590-022-01291-2
doi: 10.1038/s41590-022-01291-2
pubmed: 36002647
pmcid: 9554620
Johnson DB, Nebhan CA, Moslehi JJ, Balko JM (2022) Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol 19(4):254–267. https://doi.org/10.1038/S41571-022-00600-W
doi: 10.1038/S41571-022-00600-W
pubmed: 35082367
pmcid: 8790946
Kagamu H, Kitano S, Yamaguchi O et al (2020) CD4+ T-cell immunity in the peripheral blood correlates with response to Anti-PD-1 therapy. Cancer Immunol Res 8(3):334–344. https://doi.org/10.1158/2326-6066
doi: 10.1158/2326-6066
pubmed: 31871122
Kargl J, Busch SE, Yang GHY et al (2017) Neutrophils dominate the immune cell composition in non-small cell lung cancer. Nat Commun 8(1):1–11. https://doi.org/10.1038/ncomms14381
doi: 10.1038/ncomms14381
Kharel S, Shrestha S, Shakya P et al (2022) Prognostic significance of mean platelet volume in patients with lung cancer: a meta-analysis. J Int Med Res 50(3):1–14. https://doi.org/10.1177/03000605221084874
doi: 10.1177/03000605221084874
Khunger M, Patil PD, Khunger A et al (2018) Post-treatment changes in hematological parameters predict response to nivolumab monotherapy in non-small cell lung cancer patients. PLoS One 13(10):e0197743. https://doi.org/10.1371/journal.pone.0197743
doi: 10.1371/journal.pone.0197743
pubmed: 30359383
pmcid: 6201866
Kim SS, Sumner WA, Miyauchi S et al (2021) Role of B cells in responses to checkpoint blockade immunotherapy and overall survival of cancer patients. Clin Cancer Res 27(22):6075–6082. https://doi.org/10.1158/1078-0432.CCR-21-0697
doi: 10.1158/1078-0432.CCR-21-0697
pubmed: 34230025
pmcid: 8976464
Koh J, Hur JY, Lee KY et al (2020) Regulatory (FoxP3+) T cells and TGF-β predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer. Sci Rep 10(1):18994. https://doi.org/10.1038/s41598-020-76130-1
doi: 10.1038/s41598-020-76130-1
pubmed: 33149213
pmcid: 7642363
Kumagai S, Togashi Y, Kamada T et al (2020) The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol 21(11):1346–1358. https://doi.org/10.1038/S41590-020-0769-3
doi: 10.1038/S41590-020-0769-3
pubmed: 32868929
Lee YJ, Park YS, Lee HW et al (2022) Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer. Sci Rep 12(1):626. https://doi.org/10.1038/s41598-021-04630-9
doi: 10.1038/s41598-021-04630-9
pubmed: 35022510
pmcid: 8755768
Li Y, Zhang Z, Hu Y et al (2020) Pretreatment neutrophil-to-lymphocyte ratio (NLR) may predict the outcomes of advanced non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Front Oncol 10:654. https://doi.org/10.3389/FONC.2020.00654/BIBTEX
doi: 10.3389/FONC.2020.00654/BIBTEX
pubmed: 32656072
pmcid: 7324627
Lu S, Stein JE, Rimm DL et al (2019) Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: a systematic review and meta-analysis. JAMA Oncol 5(8):1195–1204. https://doi.org/10.1001/jamaoncol.2019.1549
doi: 10.1001/jamaoncol.2019.1549
pubmed: 31318407
pmcid: 6646995
Luchini C, Bibeau F, Ligtenberg MJL et al (2019) ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol 30(8):1232–1243. https://doi.org/10.1093/annonc/mdz116
doi: 10.1093/annonc/mdz116
pubmed: 31056702
Mareckova H, Ravdan A, Fucikova T, Janatkova I (2002) Detection of the production of intracellular cytokines by T lymphocytes using flow cytometry–methodologic problems. Epidemiol Mikrobiol Imunol 51(3):111–118
pubmed: 12184189
Marone G, Schroeder JT, Mattei F et al (2020) Is there a role for basophils in cancer? Front Immunol 11:2103. https://doi.org/10.3389/FIMMU.2020.02103
doi: 10.3389/FIMMU.2020.02103
pubmed: 33013885
pmcid: 7505934
Mathew M, Safyan RA, Shu CA (2017) PD-L1 as a biomarker in NSCLC: challenges and future directions. Ann Transl Med 5(18):375. https://doi.org/10.21037/ATM.2017.08.04
doi: 10.21037/ATM.2017.08.04
pubmed: 29057235
pmcid: 5635251
McGrail DJ, Pilié PG, Rashid NU et al (2021) High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann Oncol 32(5):661–672. https://doi.org/10.1016/j.annonc.2021.02.006
doi: 10.1016/j.annonc.2021.02.006
pubmed: 33736924
Oberg HH, Wesch D, Kalyan S, Kabelitz D (2019) Regulatory interactions between neutrophils, tumor cells and T cells. Front Immunol 10:1690. https://doi.org/10.3389/FIMMU.2019.01690
doi: 10.3389/FIMMU.2019.01690
pubmed: 31379875
pmcid: 6657370
Omar M, Tanriverdi O, Cokmert S et al (2018) Role of increased mean platelet volume (MPV) and decreased MPV/platelet count ratio as poor prognostic factors in lung cancer. Clin Respir J 12(3):922–929. https://doi.org/10.1111/CRJ.12605
doi: 10.1111/CRJ.12605
pubmed: 28026133
Parikh K, Kumar A, Ahmed J et al (2018) Peripheral monocytes and neutrophils predict response to immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer. Cancer Immunol Immunother 67(9):1365–1370. https://doi.org/10.1007/s00262-018-2192-2
doi: 10.1007/s00262-018-2192-2
pubmed: 29968154
Patel AJ, Richter A, Drayson MT, Middleton GW (2020) The role of B lymphocytes in the immuno-biology of non-small-cell lung cancer. Cancer Immunol Immunother 69(3):325–342. https://doi.org/10.1007/S00262-019-02461-2
doi: 10.1007/S00262-019-02461-2
pubmed: 31901949
pmcid: 7044257
Pawelczyk K, Piotrowska A, Ciesielska U et al (2019) Role of PD-L1 expression in non-small cell lung cancer and their prognostic significance according to clinicopathological factors and diagnostic markers. Int J Mol Sci 20(4):524. https://doi.org/10.3390/IJMS20040824
doi: 10.3390/IJMS20040824
Peranzoni E, Ingangi V, Masetto E et al (2020) Myeloid cells as clinical biomarkers for immune checkpoint blockade. Front Immunol 11:1590. https://doi.org/10.3389/fimmu.2020.01590
doi: 10.3389/fimmu.2020.01590
pubmed: 32793228
pmcid: 7393010
Pio R, Ajona D, Ortiz-Espinosa S et al (2019) Complementing the cancer-immunity cycle. Front Immunol 10:774. https://doi.org/10.3389/FIMMU.2019.00774
doi: 10.3389/FIMMU.2019.00774
pubmed: 31031765
pmcid: 6473060
Principe DR, Chiec L, Mohindra NA, Munshi HG (2021) Regulatory T-cells as an emerging barrier to immune checkpoint inhibition in lung cancer. Front Oncol 11:684098. https://doi.org/10.3389/FONC.2021.684098
doi: 10.3389/FONC.2021.684098
pubmed: 34141625
pmcid: 8204014
Roumenina LT, Daugan M, Petitprez F et al (2019) Context-dependent roles of complement in cancer. Nat Rev Cancer 19(12):698–715. https://doi.org/10.1038/s41568-019-0210-0
doi: 10.1038/s41568-019-0210-0
pubmed: 31666715
Sankar K, Ye JC, Li Z et al (2022) The role of biomarkers in personalized immunotherapy. Biomark Res 10(1):1–13. https://doi.org/10.1186/S40364-022-00378-0
doi: 10.1186/S40364-022-00378-0
Scheel AH, Ansén S, Schultheis AM et al (2016) PD-L1 expression in non-small cell lung cancer: correlations with genetic alterations. Oncoimmunology 5(5):e1131379. https://doi.org/10.1080/2162402X.2015.1131379
doi: 10.1080/2162402X.2015.1131379
pubmed: 27467949
pmcid: 4910698
Seymour L, Bogaerts J, Perrone A et al (2017) iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 18(3):e143. https://doi.org/10.1016/S1470-2045(17)30074-8
doi: 10.1016/S1470-2045(17)30074-8
pubmed: 28271869
pmcid: 5648544
Sibille A, Corhay JL, Louis R et al (2022) Eosinophils and lung cancer: from bench to bedside. Int J Mol Sci 23(9):5066. https://doi.org/10.3390/IJMS23095066
doi: 10.3390/IJMS23095066
pubmed: 35563461
pmcid: 9101877
Tazzyman S, Lewis CE, Murdoch C (2009) Neutrophils: key mediators of tumour angiogenesis. Int J Exp Pathol 90(3):222. https://doi.org/10.1111/J.1365-2613.2009.00641.X
doi: 10.1111/J.1365-2613.2009.00641.X
pubmed: 19563607
pmcid: 2697547
Thurman JM, Laskowski J, Nemeno RA (2020) Complement and cancer—a dysfunctional relationship? Antibodies 9(4):1–16. https://doi.org/10.3390/ANTIB9040061
doi: 10.3390/ANTIB9040061
Wei SC, Duffy CR, Allison JP (2018) Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov 8(9):1069–1086. https://doi.org/10.1158/2159-8290.CD-18-0367
doi: 10.1158/2159-8290.CD-18-0367
pubmed: 30115704
Wu C, Qiu Y, Zhang R et al (2022) Association of peripheral basophils with tumor M2 macrophage infiltration and outcomes of the anti-PD-1 inhibitor plus chemotherapy combination in advanced gastric cancer. J Transl Med 20(1):1–15. https://doi.org/10.1186/S12967-022-03598-Y
doi: 10.1186/S12967-022-03598-Y
Yan Y, Wang X, Liu C, Jia J (2022) Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study. BMC Pulm Med 22(1):1–14. https://doi.org/10.1186/S12890-022-01951-X
doi: 10.1186/S12890-022-01951-X
Yang Y, Li C, Liu T et al (2020) Myeloid-derived suppressor cells in tumors: from mechanisms to antigen specificity and microenvironmental regulation. Front Immunol 11:1371. https://doi.org/10.3389/FIMMU.2020.01371
doi: 10.3389/FIMMU.2020.01371
pubmed: 32793192
pmcid: 7387650
Zha H, Wang X, Zhu Y et al (2019) Intracellular activation of complement C3 leads to PD-L1 antibody treatment resistance by modulating tumor-associated macrophages. Cancer Immunol Res 7(2):193–207. https://doi.org/10.1158/2326-6066.CIR-18-0272
doi: 10.1158/2326-6066.CIR-18-0272
pubmed: 30514794
Zhang Z, Zhang F, Yuan F et al (2020) Pretreatment hemoglobin level as a predictor to evaluate the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer. Ther Adv Med Oncol 5(12):1758835920970049. https://doi.org/10.1177/1758835920970049
doi: 10.1177/1758835920970049