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Systematic profiling of immune signatures identifies prognostic predictors in lung adenocarcinoma

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Abstract

Purpose

Lung adenocarcinoma (LUAD) is the predominant subtype of lung cancer, with increasing evidence showing clinical benefits of immunotherapy. However, a lack of integrated profiles of complex LUAD immune microenvironments hampers the application of immunotherapy, resulting in limited eligible patient populations as well as drug resistance problems. Here, we aimed to systematically profile the immune signatures of LUADs and to assess the role of the immune microenvironment in patient outcome.

Methods

We systematically profiled the immune signatures of LUADs deposited in the TCGA and GEO databases using a total of 730 immune-related genes. Differential expression analysis was used to identify dysregulated genes. Univariate Cox analysis followed by robust likelihood-based survival analysis and multivariate Cox analysis were applied to construct an immune-related prognostic model.

Results

We found that differentially expressed immune genes were mainly enriched in immune cell proliferation, migration, activation and the NF-κB and TNF signaling pathways. The 10-immune gene predictive model that we constructed could differentiate LUAD patients with different overall survival times in several datasets, with areas under the curve (AUCs) of 0.67, 0.69, 0.72 and 0.74. LUAD patients with high- or low-risk scores exhibited distinct immune cell compositions, which may explain the prognostic significance of our model.

Conclusions

Our results add to the current knowledge of immune processes in LUADs and underscore the critical role of the immune microenvironment in LUAD patient outcome.

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References

  1. W. Chen, R. Zheng, P.D. Baade, S. Zhang, H. Zeng, F. Bray, A. Jemal, X.Q. Yu, J. He, Cancer statistics in China, 2015. CA Cancer J Clin 66, 115–132 (2016)

    PubMed  Google Scholar 

  2. R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2018. CA Cancer J Clin 68, 7–30 (2018)

    PubMed  Google Scholar 

  3. L.A. Torre, F. Bray, R.L. Siegel, J. Ferlay, J. Lortet-Tieulent, A. Jemal, Global cancer statistics, 2012. CA Cancer J Clin 65, 87–108 (2015)

    PubMed  Google Scholar 

  4. L. Cortes-Dericks, D. Galetta, The therapeutic potential of mesenchymal stem cells in lung cancer: Benefits, risks and challenges. Cell Oncol 42, 727–738 (2019)

    Google Scholar 

  5. A. Quintanal-Villalonga, S. Molina-Pinelo, Epigenetics of lung cancer: A translational perspective. Cell Oncol 42, 739–756 (2019)

    CAS  Google Scholar 

  6. W.D. Travis, E. Brambilla, A.G. Nicholson, Y. Yatabe, J.H.M. Austin, M.B. Beasley, L.R. Chirieac, S. Dacic, E. Duhig, D.B. Flieder, K. Geisinger, F.R. Hirsch, Y. Ishikawa, K.M. Kerr, M. Noguchi, G. Pelosi, C.A. Powell, M.S. Tsao, I. Wistuba, W.H.O. Panel, The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 10, 1243–1260 (2015)

    PubMed  Google Scholar 

  7. Z. Chen, C.M. Fillmore, P.S. Hammerman, C.F. Kim, K.K. Wong, Non-small-cell lung cancers: A heterogeneous set of diseases. Nat Rev Cancer 14, 535–546 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  8. J. Rotow, T.G. Bivona, Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer 17, 637–658 (2017)

    CAS  PubMed  Google Scholar 

  9. A. Ribas, J.D. Wolchok, Cancer immunotherapy using checkpoint blockade. Science 359, 1350–1355 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  10. A. Ghahremanloo, A. Soltani, S.M.S. Modaresi, S.I. Hashemy, Recent advances in the clinical development of immune checkpoint blockade therapy. Cell Oncol 42, 609–626 (2019)

    Google Scholar 

  11. L. Gandhi, D. Rodriguez-Abreu, S. Gadgeel, E. Esteban, E. Felip, F. De Angelis, M. Domine, P. Clingan, M.J. Hochmair, S.F. Powell, S.Y. Cheng, H.G. Bischoff, N. Peled, F. Grossi, R.R. Jennens, M. Reck, R. Hui, E.B. Garon, M. Boyer, B. Rubio-Viqueira, S. Novello, T. Kurata, J.E. Gray, J. Vida, Z. Wei, J. Yang, H. Raftopoulos, M.C. Pietanza, M.C. Garassino, K. Investigators, Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378, 2078–2092 (2018)

  12. H. Borghaei, L. Paz-Ares, L. Horn, D.R. Spigel, M. Steins, N.E. Ready, L.Q. Chow, E.E. Vokes, E. Felip, E. Holgado, F. Barlesi, M. Kohlhaufl, O. Arrieta, M.A. Burgio, J. Fayette, H. Lena, E. Poddubskaya, D.E. Gerber, S.N. Gettinger, C.M. Rudin, N. Rizvi, L. Crino, G.R. Blumenschein Jr., S.J. Antonia, C. Dorange, C.T. Harbison, F. Graf Finckenstein, J.R. Brahmer, Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373, 1627–1639 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  13. J.C.H. Chow, K.M. Cheung, W.C.S. Cho, Atezolizumab in non-small cell lung cancer: The era of precision immuno-oncology. Ann Transl Med 5, 265 (2017)

    PubMed  PubMed Central  Google Scholar 

  14. P.C. Tumeh, C.L. Harview, J.H. Yearley, I.P. Shintaku, E.J. Taylor, L. Robert, B. Chmielowski, M. Spasic, G. Henry, V. Ciobanu, A.N. West, M. Carmona, C. Kivork, E. Seja, G. Cherry, A.J. Gutierrez, T.R. Grogan, C. Mateus, G. Tomasic, J.A. Glaspy, R.O. Emerson, H. Robins, R.H. Pierce, D.A. Elashoff, C. Robert, A. Ribas, PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568–571 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. S. Spranger, T.F. Gajewski, Impact of oncogenic pathways on evasion of antitumour immune responses. Nat Rev Cancer 18, 139–147 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. R.S. Herbst, J.C. Soria, M. Kowanetz, G.D. Fine, O. Hamid, M.S. Gordon, J.A. Sosman, D.F. McDermott, J.D. Powderly, S.N. Gettinger, H.E. Kohrt, L. Horn, D.P. Lawrence, S. Rost, M. Leabman, Y. Xiao, A. Mokatrin, H. Koeppen, P.S. Hegde, I. Mellman, D.S. Chen, F.S. Hodi, Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515, 563–567 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Naiyer A. Rizvi, Matthew D. Hellmann, Alexandra Snyder, Pia Kvistborg, Vladimir Makarov, Jonathan J. Havel, William Lee, Jianda Yuan, Phillip Wong, Teresa S. Ho, Martin L. Miller, Natasha Rekhtman, Andre L. Moreira, Fawzia Ibrahim, Cameron Bruggeman, Billel Gasmi, Roberta Zappasodi, Yuka Maeda, Chris Sander, Edward B. Garon, Taha Merghoub, Jedd D. Wolchok, Ton N. Schumacher and T.A. Chan, Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 348, 124–128 (2016)

  18. D.T. Le, J.N. Uram, H. Wang, B.R. Bartlett, H. Kemberling, A.D. Eyring, A.D. Skora, B.S. Luber, N.S. Azad, D. Laheru, B. Biedrzycki, R.C. Donehower, A. Zaheer, G.A. Fisher, T.S. Crocenzi, J.J. Lee, S.M. Duffy, R.M. Goldberg, A. de la Chapelle, M. Koshiji, F. Bhaijee, T. Huebner, R.H. Hruban, L.D. Wood, N. Cuka, D.M. Pardoll, N. Papadopoulos, K.W. Kinzler, S. Zhou, T.C. Cornish, J.M. Taube, R.A. Anders, J.R. Eshleman, B. Vogelstein, L.A. Diaz Jr., PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372, 2509–2520 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  19. H. Tang, Y. Wang, L.K. Chlewicki, Y. Zhang, J. Guo, W. Liang, J. Wang, X. Wang, Y.X. Fu, Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell 29, 285–296 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  20. S. Zheng, X. Luo, C. Dong, D. Zheng, J. Xie, L. Zhuge, Y. Sun, H. Chen, A B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma. Int J Cancer 143, 2592–2601 (2018)

    CAS  PubMed  Google Scholar 

  21. H. Faruki, G.M. Mayhew, J.S. Serody, D.N. Hayes, C.M. Perou, M. Lai-Goldman, Lung adenocarcinoma and squamous cell carcinoma gene expression subtypes demonstrate significant differences in tumor immune landscape. J Thorac Oncol 12, 943–953 (2017)

    PubMed  PubMed Central  Google Scholar 

  22. M.B. Schabath, E.A. Welsh, W.J. Fulp, L. Chen, J.K. Teer, Z.J. Thompson, B.E. Engel, M. Xie, A.E. Berglund, B.C. Creelan, S.J. Antonia, J.E. Gray, S.A. Eschrich, D.T. Chen, W.D. Cress, E.B. Haura, A.A. Beg, Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene 35, 3209–3216 (2016)

    CAS  PubMed  Google Scholar 

  23. Q. Song, J. Shang, Z. Yang, L. Zhang, C. Zhang, J. Chen, X. Wu, Identification of an immune signature predicting prognosis risk of patients in lung adenocarcinoma. J Transl Med 17, 70 (2019)

    PubMed  PubMed Central  Google Scholar 

  24. J.K. HyungJun Cho, A. Yu, S. Kim, S.-M. Hong, Robust likelihood-based survival modeling with microarray data. J Statistical Software 29 (2009)

  25. A.M. Newman, C.L. Liu, M.R. Green, A.J. Gentles, W. Feng, Y. Xu, C.D. Hoang, M. Diehn, A.A. Alizadeh, Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 12, 453–457 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  26. M. Uhlén, L. Fagerberg, B.M. Hallström, C. Lindskog, P. Oksvold, A. Mardinoglu, Å. Sivertsson, C. Kampf, E. Sjöstedt, A. Asplund, I.M. Olsson, K. Edlund, E. Lundberg, S. Navani, C.A.-K. Szigyarto, J. Odeberg, D. Djureinovic, J.O. Takanen, S. Hober, T. Alm, P.-H. Edqvist, H. Berling, H. Tegel, J. Mulder, J. Rockberg, P. Nilsson, J.M. Schwenk, M. Hamsten, K. von Feilitzen, M. Forsberg, L. Persson, F. Johansson, M. Zwahlen, G. von Heijne, J. Nielsen, F. Pontén, Tissue-based map of the human proteome. Science 34, 1260419 (2015)

  27. G. Pascual, A. Avgustinova, S. Mejetta, M. Martin, A. Castellanos, C.S. Attolini, A. Berenguer, N. Prats, A. Toll, J.A. Hueto, C. Bescos, L. Di Croce, S.A. Benitah, Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 541, 41–45 (2017)

    CAS  PubMed  Google Scholar 

  28. A. Ladanyi, A. Mukherjee, H.A. Kenny, A. Johnson, A.K. Mitra, S. Sundaresan, K.M. Nieman, G. Pascual, S.A. Benitah, A. Montag, S.D. Yamada, N.A. Abumrad, E. Lengyel, Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis. Oncogene 37, 2285–2301 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  29. J. Pan, Z. Fan, Z. Wang, Q. Dai, Z. Xiang, F. Yuan, M. Yan, Z. Zhu, B. Liu, C. Li, CD36 mediates palmitate acid-induced metastasis of gastric cancer via AKT/GSK-3beta/beta-catenin pathway. Journal of experimental & clinical cancer research : CR 38, 52 (2019)

    PubMed Central  Google Scholar 

  30. J. Couzin-Frankel, Breakthrough of the year 2013. Cancer immunotherapy Science 342, 1432–1433 (2013)

    CAS  PubMed  Google Scholar 

  31. A. Rittmeyer, F. Barlesi, D. Waterkamp, K. Park, F. Ciardiello, J. von Pawel, S.M. Gadgeel, T. Hida, D.M. Kowalski, M.C. Dols, D.L. Cortinovis, J. Leach, J. Polikoff, C. Barrios, F. Kabbinavar, O.A. Frontera, F. De Marinis, H. Turna, J.-S. Lee, M. Ballinger, M. Kowanetz, P. He, D.S. Chen, A. Sandler, D.R. Gandara, Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet 389, 255–265 (2017)

    PubMed  Google Scholar 

  32. E.B. Garon, N.A. Rizvi, R. Hui, N. Leighl, A.S. Balmanoukian, J.P. Eder, A. Patnaik, C. Aggarwal, M. Gubens, L. Horn, E. Carcereny, M.J. Ahn, E. Felip, J.S. Lee, M.D. Hellmann, O. Hamid, J.W. Goldman, J.C. Soria, M. Dolled-Filhart, R.Z. Rutledge, J. Zhang, J.K. Lunceford, R. Rangwala, G.M. Lubiniecki, C. Roach, K. Emancipator, L. Gandhi, K. Investigators, Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372, 2018–2028 (2015)

  33. J. Brahmer, K.L. Reckamp, P. Baas, L. Crino, W.E. Eberhardt, E. Poddubskaya, S. Antonia, A. Pluzanski, E.E. Vokes, E. Holgado, D. Waterhouse, N. Ready, J. Gainor, O. Aren Frontera, L. Havel, M. Steins, M.C. Garassino, J.G. Aerts, M. Domine, L. Paz-Ares, M. Reck, C. Baudelet, C.T. Harbison, B. Lestini, D.R. Spigel, Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373, 123–135 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  34. W.H. Fridman, F. Pages, C. Sautes-Fridman, J. Galon, The immune contexture in human tumours: Impact on clinical outcome. Nat Rev Cancer 12, 298–306 (2012)

    CAS  PubMed  Google Scholar 

  35. D.S. Thommen, T.N. Schumacher, T cell dysfunction in cancer. Cancer Cell 33, 547–562 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  36. S.K. Biswas, A. Mantovani, Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat Immunol 11, 889 (2010)

    CAS  PubMed  Google Scholar 

  37. A. Mantovani, S. Sozzani, M. Locati, P. Allavena, A. Sica, Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23, 549–555 (2002)

    CAS  PubMed  Google Scholar 

  38. A. Salmaninejad, S.F. Valilou, A. Soltani, S. Ahmadi, Y.J. Abarghan, R.J. Rosengren, A. Sahebkar, Tumor-associated macrophages: Role in cancer development and therapeutic implications. Cell Oncol 42, 591–608 (2019)

    Google Scholar 

  39. M. Karin, Y. Cao, F.R. Greten, Z.W. Li, NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer 2, 301–310 (2002)

    CAS  PubMed  Google Scholar 

  40. Y. Grinberg-Bleyer, H. Oh, A. Desrichard, D.M. Bhatt, R. Caron, T.A. Chan, R.M. Schmid, U. Klein, M.S. Hayden, S. Ghosh, NF-kappaB c-Rel is crucial for the regulatory T cell immune checkpoint in cancer. Cell 170, 1096, e1013–1108 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  41. K. Taniguchi, M. Karin, NF-kappaB, inflammation, immunity and cancer: Coming of age. Nat Rev Immunol 18, 309–324 (2018)

    CAS  PubMed  Google Scholar 

  42. R.L. Silverstein and M. Febbraio, CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal 2, re3 (2009)

  43. T.K. Means, E. Mylonakis, E. Tampakakis, R.A. Colvin, E. Seung, L. Puckett, M.F. Tai, C.R. Stewart, R. Pukkila-Worley, S.E. Hickman, K.J. Moore, S.B. Calderwood, N. Hacohen, A.D. Luster, J. El Khoury, Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med 206, 637–653 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  44. By Matthew L. Albert, S. Frieda A., Pearce, Loise M. Francisco, Birthe Sauter, Pampa Roy, Roy L. Silverstein and N. Bhardwaj, immature dendritic cells phagocytose apoptotic cells via avb5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188, 1359–1368 (1998)

  45. Q. Sun, W. Zhang, L. Wang, F. Guo, D. Song, Q. Zhang, D. Zhang, Y. Fan, J. Wang, Hypermethylated CD36 gene affected the progression of lung cancer. Gene 678, 395–406 (2018)

    CAS  PubMed  Google Scholar 

  46. R.A. DeFilippis, H. Chang, N. Dumont, J.T. Rabban, Y.Y. Chen, G.V. Fontenay, H.K. Berman, M.L. Gauthier, J. Zhao, D. Hu, J.J. Marx, J.A. Tjoe, E. Ziv, M. Febbraio, K. Kerlikowske, B. Parvin, T.D. Tlsty, CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues. Cancer Discov 2, 826–839 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  47. X. Zhang, J. Yao, H. Shi, B. Gao, L. Zhang, LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis. Biol Chem 400, 663–675 (2019)

    CAS  PubMed  Google Scholar 

  48. A. Nath, C. Chan, Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers. Sci Rep 6, 18669 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  49. H.L. Huang, Y.C. Wu, L.J. Su, Y.J. Huang, P. Charoenkwan, W.L. Chen, H.C. Lee, W.C. Chu, S.Y. Ho, Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data. BMC Bioinformatics 16, 54 (2015)

    PubMed  PubMed Central  Google Scholar 

  50. D.E. Johnson, R.A. O'Keefe, J.R. Grandis, Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 15, 234–248 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  51. G. Srikrishna, S100A8 and S100A9: New insights into their roles in malignancy. J Innate Immun 4, 31–40 (2012)

    CAS  PubMed  Google Scholar 

  52. F. Shabani, A. Farasat, M. Mahdavi, N. Gheibi, Calprotectin (S100A8/S100A9): A key protein between inflammation and cancer. Inflamm Res 67, 801–812 (2018)

    CAS  PubMed  Google Scholar 

  53. G.E. White, A.J. Iqbal, D.R. Greaves, CC chemokine receptors and chronic inflammation--therapeutic opportunities and pharmacological challenges. Pharmacol Rev 65, 47–89 (2013)

    CAS  PubMed  Google Scholar 

  54. U.H. Weidle, S. Klostermann, D. Eggle, A. Kruger, Interleukin 6/interleukin 6 receptor interaction and its role as a therapeutic target for treatment of cachexia and cancer. Cancer Genomics Proteomics 7, 287–302 (2010)

    CAS  PubMed  Google Scholar 

  55. H. Nakamura, S. Dan, T. Akashi, M. Unno, T. Yamori, Absolute quantification of four isoforms of the class I phosphoinositide-3-kinase catalytic subunit by real-time RT-PCR. Biol Pharm Bull 30, 1181–1184 (2007)

    CAS  PubMed  Google Scholar 

  56. K. Liu, K. Yang, B. Wu, H. Chen, X. Chen, X. Chen, L. Jiang, F. Ye, D. He, Z. Lu, L. Xue, W. Zhang, Q. Li, Z. Zhou, X. Mo, J. Hu, Tumor-infiltrating immune cells are associated with prognosis of gastric cancer. Medicine (Baltimore) 94, e1631 (2015)

  57. J. Galon, A. Costes, F. Sanchez-Cabo, A. Kirilovsky, B. Mlecnik, C. Lagorce-Page’s, M. Tosolini, M. Camus, A. Berger, P. Wind, F. Zinzindohoue, P. Bruneval, P-H. Cugnenc, Z. Trajanoski, W-H. Fridman, F. Page’s, Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960-1964 (2006)

  58. M.R. Tian Tian, Wentao Yang, Ruohong Shui. Evaluation of the prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers. Oncotarget 7, 27323808 (2016)

  59. E. Brambilla, G. Le Teuff, S. Marguet, S. Lantuejoul, A. Dunant, S. Graziano, R. Pirker, J.Y. Douillard, T. Le Chevalier, M. Filipits, R. Rosell, R. Kratzke, H. Popper, J.C. Soria, F.A. Shepherd, L. Seymour, M.S. Tsao, Prognostic effect of tumor lymphocytic infiltration in Resectable non-small-cell lung cancer. J Clin Oncol 34, 1223–1230 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  60. D. Argyle, T. Kitamura, Targeting macrophage-recruiting chemokines as a novel therapeutic strategy to prevent the progression of solid tumors. Front Immunol 9, 2629 (2018)

    PubMed  PubMed Central  Google Scholar 

  61. C.E.M. Aarts and T.W. Kuijpers, Neutrophils as myeloid-derived suppressor cells. Eur J Clin Invest 48 Suppl 2, e12989 (2018)

  62. J. Borst, T. Ahrends, N. Babala, C.J.M. Melief, W. Kastenmuller, CD4(+) T cell help in cancer immunology and immunotherapy. Nat Rev Immunol 18, 635–647 (2018)

    CAS  PubMed  Google Scholar 

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Acknowledgements

The work was supported by the National Natural Science Foundation of China (81802299, 81502514), the CAMS Science Foundation for Young Scientists (3332018070), the CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001, 2017-I2M-1-005) and the National Key Basic Research Development Plan (2018YFC1312105).

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  1. Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Shuangshuang Mao, Yuan Li, Zhiliang Lu, Yun Che, Jianbing Huang, Yuanyuan Lei, Yalong Wang, Xinfeng Wang, Chengming Liu, Sufei Zheng, Ning Li, Jiagen Li, Nan Sun & Jie He

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Mao, S., Li, Y., Lu, Z. et al. Systematic profiling of immune signatures identifies prognostic predictors in lung adenocarcinoma. Cell Oncol. 43, 681–694 (2020). https://doi.org/10.1007/s13402-020-00515-7

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