Platelet PD-L1 reflects collective intratumoral PD-L1 expression and predicts immunotherapy response in non-small cell lung cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
20
05
2021
accepted:
09
11
2021
entrez:
2
12
2021
pubmed:
3
12
2021
medline:
29
12
2021
Statut:
epublish
Résumé
Immune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers to predict therapy response are missing. Here we show that blood platelets interact with lung cancer cells and that PD-L1 protein is transferred from tumor cells to platelets in a fibronectin 1, integrin α5β1 and GPIbα-dependent manner. Platelets from NSCLC patients are found to express PD-L1 and platelet PD-L1 possess the ability to inhibit CD4 and CD8 T-cells. An algorithm is developed to calculate the activation independent adjusted PD-L1 payload of platelets (pPD-L1
Identifiants
pubmed: 34853305
doi: 10.1038/s41467-021-27303-7
pii: 10.1038/s41467-021-27303-7
pmc: PMC8636618
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
Immunologic Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7005Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Nishimura, H. et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291, 319–322 (2001).
pubmed: 11209085
doi: 10.1126/science.291.5502.319
Ueda, H. et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423, 506–511 (2003).
pubmed: 12724780
doi: 10.1038/nature01621
Leach, D. R., Krummel, M. F. & Allison, J. P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734–1736 (1996).
pubmed: 8596936
doi: 10.1126/science.271.5256.1734
Ishida, Y., Agata, Y., Shibahara, K. & Honjo, T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11, 3887–3895 (1992).
pubmed: 1396582
pmcid: 556898
doi: 10.1002/j.1460-2075.1992.tb05481.x
Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).
pubmed: 20525992
pmcid: 3549297
doi: 10.1056/NEJMoa1003466
Herbst, R. S. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387, 1540–50 (2016).
pubmed: 26712084
doi: 10.1016/S0140-6736(15)01281-7
Reck, M. et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 375, 1823–33 (2016).
pubmed: 27718847
doi: 10.1056/NEJMoa1606774
Yau, T. et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol. 6, e204564 (2020).
Carbone, D. P. et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N. Engl. J. Med. 376, 2415–26 (2017).
pubmed: 28636851
pmcid: 6487310
doi: 10.1056/NEJMoa1613493
Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J. Clin. 68, 394–424 (2018).
Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer Statistics, 2021. CA: Cancer J. Clin. 71, 7–33 (2021).
Teng, F., Meng, X., Kong, L. & Yu, J. Progress and challenges of predictive biomarkers of anti PD-1/PD-L1 immunotherapy: a systematic review. Cancer Lett. 414, 166–73 (2018).
pubmed: 29155348
doi: 10.1016/j.canlet.2017.11.014
Herbst, R. S. et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515, 563–567 (2014).
pubmed: 25428504
pmcid: 4836193
doi: 10.1038/nature14011
Taube, J. M. 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. 20, 5064–5074 (2014).
pubmed: 24714771
pmcid: 4185001
doi: 10.1158/1078-0432.CCR-13-3271
Champiat, S., Ferte, C., Lebel-Binay, S., Eggermont, A. & Soria, J. C. Exomics and immunogenics: Bridging mutational load and immune checkpoints efficacy. Oncoimmunology 3, e27817 (2014).
pubmed: 24605269
pmcid: 3937193
doi: 10.4161/onci.27817
Warshaw, A. L., Laster, L. & Shulman, N. R. The stimulation by thrombin of glucose oxidation in human platelets. J. Clin. Invest. 45, 1923–1934 (1966).
pubmed: 4959090
pmcid: 292878
doi: 10.1172/JCI105497
Warshaw, A. L., Laster, L. & Shulman, N. R. Protein synthesis by human platelets. J. Biol. Chem. 242, 2094–2097 (1967).
pubmed: 6022853
doi: 10.1016/S0021-9258(18)96021-7
Weyrich, A. S. et al. Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets. Proc. Natl Acad. Sci. USA 95, 5556–5561 (1998).
pubmed: 9576921
pmcid: 20416
doi: 10.1073/pnas.95.10.5556
Evangelista, V. et al. De novo synthesis of cyclooxygenase-1 counteracts the suppression of platelet thromboxane biosynthesis by aspirin. Circ. Res. 98, 593–595 (2006).
pubmed: 16484611
doi: 10.1161/01.RES.0000214553.37930.3e
Schneider-Poetsch, T. et al. Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat. Chem. Biol. 6, 209–17 (2010).
pubmed: 20118940
pmcid: 2831214
doi: 10.1038/nchembio.304
Cho, J. & Mosher, D. F. Role of fibronectin assembly in platelet thrombus formation. J. Thromb. Haemost. 4, 1461–1469 (2006).
pubmed: 16839338
doi: 10.1111/j.1538-7836.2006.01943.x
Zeiler, M., Moser, M. & Mann, M. Copy number analysis of the murine platelet proteome spanning the complete abundance range. Mol. Cell Proteom. 13, 3435–3445 (2014).
doi: 10.1074/mcp.M114.038513
Grassme, H., Bock, J., Kun, J. & Gulbins, E. Clustering of CD40 ligand is required to form a functional contact with CD40. J. Biol. Chem. 277, 30289–30299 (2002).
pubmed: 12011072
doi: 10.1074/jbc.M200494200
Metelli, A. et al. Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β. Sci Transl Med. 12, eaay4860 (2020).
Rachidi, S. et al. Platelets subvert T cell immunity against cancer via GARP-TGFβ axis. Sci Immunol. 2, eaai7911 (2017).
Kim, S. H. et al. Expression of cancer-testis antigens MAGE-A3/6 and NY-ESO-1 in non-small-cell lung carcinomas and their relationship with immune cell infiltration. Lung 187, 401–411 (2009).
pubmed: 19795170
doi: 10.1007/s00408-009-9181-3
Mussbacher, M. et al. Optimized plasma preparation is essential to monitor platelet-stored molecules in humans. PLoS ONE 12, e0188921 (2017).
pubmed: 29220362
pmcid: 5722331
doi: 10.1371/journal.pone.0188921
Hechler, B., Dupuis, A., Mangin, P. H. & Gachet, C. Platelet preparation for function testing in the laboratory and clinic: Historical and practical aspects. Res. Pr. Thromb. Haemost. 3, 615–25 (2019).
doi: 10.1002/rth2.12240
Skoulidis, F. & Heymach, J. V. Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat. Rev. Cancer 19, 495–509 (2019).
pubmed: 31406302
pmcid: 7043073
doi: 10.1038/s41568-019-0179-8
Kortlever, R. M. et al. Myc cooperates with Ras by programming inflammation and immune suppression. Cell 171, 1301–1315.e14 (2017).
pubmed: 29195074
pmcid: 5720393
doi: 10.1016/j.cell.2017.11.013
Liu, C. et al. The superior efficacy of anti-PD-1/PD-L1 immunotherapy in KRAS-mutant non-small cell lung cancer that correlates with an inflammatory phenotype and increased immunogenicity. Cancer Lett. 470, 95–105 (2020).
pubmed: 31644929
doi: 10.1016/j.canlet.2019.10.027
Rolfes, V. et al. PD-L1 is expressed on human platelets and is affected by immune checkpoint therapy. Oncotarget 9, 27460–70 (2018).
pubmed: 29937998
pmcid: 6007942
doi: 10.18632/oncotarget.25446
Eisenhauer, E. A. et al. noce response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009).
pubmed: 19097774
doi: 10.1016/j.ejca.2008.10.026
Seymour, L. et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 18, e143–e52 (2017).
pubmed: 28271869
pmcid: 5648544
doi: 10.1016/S1470-2045(17)30074-8
Zaslavsky, A. B. et al. Platelet PD-L1 suppresses anti-cancer immune cell activity in PD-L1 negative tumors. Sci. Rep. 10, 19296 (2020).
pubmed: 33168847
pmcid: 7652857
doi: 10.1038/s41598-020-76351-4
Draga, P. E. et al. PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer. PLoS ONE 16, e0260124 (2021).
doi: 10.1371/journal.pone.0260124
Mammadova-Bach, E. et al. Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell-derived ADAM9. JCI Insight 1, e88245 (2016).
pubmed: 27699237
pmcid: 5033851
doi: 10.1172/jci.insight.88245
Pearlstein, E., Salk, P. L., Yogeeswaran, G. & Karpatkin, S. Correlation between spontaneous metastatic potential, platelet-aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic-variant derivatives of a rat renal sarcoma cell line. Proc. Natl Acad. Sci. USA 77, 4336–4339 (1980).
pubmed: 6933486
pmcid: 349829
doi: 10.1073/pnas.77.7.4336
Heinmöller, E. et al. Studies on tumor-cell-induced platelet aggregation in human lung cancer cell lines. J. Cancer Res Clin. Oncol. 122, 735–744 (1996).
pubmed: 8954171
doi: 10.1007/BF01209121
Bastida, E., Escolar, G., Almirall, L. & Ordinas, A. Platelet activation induced by a human neuroblastoma tumor cell line is reduced by prior administration of ticlopidine. Thromb. Haemost. 55, 333–337 (1986).
pubmed: 3750263
doi: 10.1055/s-0038-1661558
Placke, T. et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res. 72, 440–448 (2012).
pubmed: 22127925
doi: 10.1158/0008-5472.CAN-11-1872
Blair, P. & Flaumenhaft, R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev. 23, 177–189 (2009).
pubmed: 19450911
pmcid: 2720568
doi: 10.1016/j.blre.2009.04.001
Zito Marino, F. et al. Heterogeneity of PD-L1 Expression in Lung Mixed Adenocarcinomas and Adenosquamous Carcinomas. Am. J. Surg. Pathol. 44, 378–86 (2020).
pubmed: 31688140
doi: 10.1097/PAS.0000000000001400
Cascone, T. W. W. et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study. J Clin Oncol. 37, 8504 (2019).
Ren, S., Wang, C., Shen, J. & Zhu, C. Neoadjuvant immunotherapy with resectable non-small cell lung cancer: recent advances and future challenges. J. Thorac. Dis. 12, 1615–1620 (2020).
pubmed: 32395299
pmcid: 7212126
doi: 10.21037/jtd.2020.03.44
Schroeder, B. O. et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469, 419–423 (2011).
pubmed: 21248850
doi: 10.1038/nature09674
Riess, T. et al. Bartonella adhesin a mediates a proangiogenic host cell response. J. Exp. Med. 200, 1267–1278 (2004).
pubmed: 15534369
pmcid: 2211922
doi: 10.1084/jem.20040500
Jurasz, P., Alonso-Escolano, D. & Radomski, M. W. Platelet–cancer interactions: mechanisms and pharmacology of tumour cell-induced platelet aggregation. Br. J. Pharm. 143, 819–826 (2004).
doi: 10.1038/sj.bjp.0706013
Widenmeyer, M. et al. Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients. Int J. Cancer 131, 140–149 (2012).
pubmed: 21858810
doi: 10.1002/ijc.26365
Kayser, S. et al. Rapid generation of NY-ESO-1-specific CD4(+) THELPER1 cells for adoptive T-cell therapy. Oncoimmunology 4, e1002723 (2015).
pubmed: 26155389
pmcid: 4485840
doi: 10.1080/2162402X.2014.1002723
Feuchtinger, T. et al. Clinical grade generation of hexon-specific T cells for adoptive T-cell transfer as a treatment of adenovirus infection after allogeneic stem cell transplantation. J. Immunother. 31, 199–206 (2008).
pubmed: 18481389
doi: 10.1097/CJI.0b013e31815ef862