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Immune-Related Adverse Events: Pneumonitis

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Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 995))

Abstract

Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis.

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References

  1. Ahmad AS, Ormiston-Smith N, Sasieni PD. Trends in the lifetime risk of developing cancer in Great Britain: comparison of risk for those born from 1930 to 1960. Br J Cancer. 2015;112(5):943–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–89.

    Article  PubMed  Google Scholar 

  3. Baxevanis CN, Perez SA, Papamichail M. Cancer immunotherapy. Crit Rev Clin Lab Sci. 2009;46(4):167–89.

    Article  CAS  PubMed  Google Scholar 

  4. Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 2016;14:73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Dillman RO. Cancer immunotherapy. Cancer Biother Radiopharm. 2011;26(1):1–64.

    Article  CAS  PubMed  Google Scholar 

  6. Oiseth SJ, Aziz MS. Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. J Cancer Metastasis Treat. 2017;3(10):250–61.

    Article  Google Scholar 

  7. Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012;23(Suppl 8):viii6–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682–7.

    Article  CAS  PubMed  Google Scholar 

  10. Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.

    Article  CAS  PubMed  Google Scholar 

  12. Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci. 2011;1217:45–59.

    Article  CAS  PubMed  Google Scholar 

  13. 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. 1992;11(11):3887–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Riley JL. PD-1 signaling in primary T cells. Immunol Rev. 2009;229(1):114–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–8.

    Article  CAS  PubMed  Google Scholar 

  18. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Amarnath S, Mangus CW, Wang JC, Wei F, He A, Kapoor V, et al. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med. 2011;3(111):111ra20.

    Article  CAS  Google Scholar 

  20. Wang X, Teng F, Kong L, Yu J. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther. 2016;9:5023–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sharpe AH, Abbas AK. T-cell costimulation—biology, therapeutic potential, and challenges. N Engl J Med. 2006;355(10):973–5.

    Article  CAS  PubMed  Google Scholar 

  24. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002;3(7):611–8.

    Article  CAS  PubMed  Google Scholar 

  25. Teft WA, Kirchhof MG, Madrenas J. A molecular perspective of CTLA-4 function. Annu Rev Immunol. 2006;24:65–97.

    Article  CAS  PubMed  Google Scholar 

  26. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182(2):459–65.

    Article  CAS  PubMed  Google Scholar 

  27. Walunas TL, Bakker CY, Bluestone JA. CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med. 1996;183(6):2541–50.

    Article  CAS  PubMed  Google Scholar 

  28. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3(5):541–7.

    Article  CAS  PubMed  Google Scholar 

  29. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270(5238):985–8.

    Article  CAS  PubMed  Google Scholar 

  30. Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1(5):405–13.

    Article  CAS  PubMed  Google Scholar 

  31. Darrasse-Jèze G, Deroubaix S, Mouquet H, Victora GD, Eisenreich T, Yao K-H, et al. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J Exp Med. 2009;206(9):1853.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Mandelbrot DA, McAdam AJ, Sharpe AH. B7-1 or B7-2 is required to produce the lymphoproliferative phenotype in mice lacking cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). J Exp Med. 1999;189(2):435–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Piccirillo CA, Shevach EM. Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol. 2004;16(2):81–8.

    Article  CAS  PubMed  Google Scholar 

  34. Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12):e731–e41.

    Article  PubMed  Google Scholar 

  35. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ramagopal UA, Liu W, Garrett-Thomson SC, Bonanno JB, Yan Q, Srinivasan M, et al. Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab. Proc Natl Acad Sci U S A. 2017;114(21):E4223–E32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tan S, Zhang H, Chai Y, Song H, Tong Z, Wang Q, et al. An unexpected N-terminal loop in PD-1 dominates binding by nivolumab. Nat Commun. 2017;8:14369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tan S, Chen D, Liu K, He M, Song H, Shi Y, et al. Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies. Protein Cell. 2016;7(12):866–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Antoniou KM, Margaritopoulos GA, Tomassetti S, Bonella F, Costabel U, Poletti V. Interstitial lung disease. Eur Respir Rev. 2014;23(131):40–54.

    Article  PubMed  Google Scholar 

  41. Lim G, Lee KH, Jeong SW, Uh S, Jin SY, Lee DH, et al. Clinical features of interstitial lung diseases. Korean J Intern Med. 1996;11(2):113–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Glasser SW, Hardie WD, Hagood JS. Pathogenesis of interstitial lung disease in children and adults. Pediatr Allergy Immunol Pulmonol. 2010;23(1):9–14.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, et al. PD-1 inhibitor-related pneumonitis in advanced Cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Epler GR. Bronchiolitis obliterans organizing pneumonia: definition and clinical features. Chest. 1992;102(1 Suppl):2S–6S.

    Article  CAS  PubMed  Google Scholar 

  45. Epler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med. 1985;312(3):152–8.

    Article  CAS  PubMed  Google Scholar 

  46. Cordier JF, Loire R, Brune J. Idiopathic bronchiolitis obliterans organizing pneumonia. Definition of characteristic clinical profiles in a series of 16 patients. Chest. 1989;96(5):999–1004.

    Article  CAS  PubMed  Google Scholar 

  47. Guerry-Force ML, Muller NL, Wright JL, Wiggs B, Coppin C, Pare PD, et al. A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial pneumonia, and small airways disease. Am Rev Respir Dis. 1987;135(3):705–12.

    CAS  PubMed  Google Scholar 

  48. King T Jr. Organizing pneumonia. In: Schwarz M, King T, editors. Interstitial lung disease. Shelton, CT: People’s Medical Publishing House; 2011.

    Google Scholar 

  49. Cordier JF. Organising pneumonia. Thorax. 2000;55(4):318–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cordier JF. Cryptogenic organising pneumonia. Eur Respir J. 2006;28(2):422–46.

    Article  PubMed  Google Scholar 

  51. Godoy MCB, Viswanathan C, Marchiori E, Truong MT, Benveniste MF, Rossi S, et al. The reversed halo sign: update and differential diagnosis. Br J Radiol. 2012;85(1017):1226–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016;2(10):1346–53.

    Article  PubMed  Google Scholar 

  53. Wells AU, Hirani N. Interstitial lung disease guideline. Thorax. 2008;63(Suppl 5):v1–v58.

    Article  PubMed  Google Scholar 

  54. Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008;63(Suppl 5):v1–58.

    PubMed  Google Scholar 

  55. Pathak V, Kuhn JM, Durham C, Funkhouser WK, Henke DC. Macrolide use leads to clinical and radiological improvement in patients with cryptogenic organizing pneumonia. Ann Am Thorac Soc. 2014;11(1):87–91.

    Article  CAS  PubMed  Google Scholar 

  56. Ding QL, Lv D, Wang BJ, Zhang QL, Yu YM, Sun SF, et al. Macrolide therapy in cryptogenic organizing pneumonia: a case report and literature review. Exp Ther Med. 2015;9(3):829–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Purcell IF, Bourke SJ, Marshall SM. Cyclophosphamide in severe steroid-resistant bronchiolitis obliterans organizing pneumonia. Respir Med. 1997;91(3):175–7.

    Article  CAS  PubMed  Google Scholar 

  58. Koinuma D, Miki M, Ebina M, Tahara M, Hagiwara K, Kondo T, et al. Successful treatment of a case with rapidly progressive Bronchiolitis obliterans organizing pneumonia (BOOP) using cyclosporin A and corticosteroid. Intern Med. 2002;41(1):26–9.

    Article  PubMed  Google Scholar 

  59. Romagnoli M, Nannini C, Piciucchi S, Girelli F, Gurioli C, Casoni G, et al. Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders? Eur Respir J. 2011;38(2):384–91.

    Article  CAS  PubMed  Google Scholar 

  60. Park IN, Jegal Y, Kim DS, Do KH, Yoo B, Shim TS, et al. Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia. Eur Respir J. 2009;33(1):68–76.

    Article  CAS  PubMed  Google Scholar 

  61. Silva CI, Muller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, et al. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology. 2008;246(1):288–97.

    Article  PubMed  Google Scholar 

  62. Travis WD, Hunninghake G, King TE Jr, Lynch DA, Colby TV, Galvin JR, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med. 2008;177(12):1338–47.

    Article  PubMed  Google Scholar 

  63. Akira M, Inoue Y, Kitaichi M, Yamamoto S, Arai T, Toyokawa K. Usual interstitial pneumonia and nonspecific interstitial pneumonia with and without concurrent emphysema: thin-section CT findings. Radiology. 2009;251(1):271–9.

    Article  PubMed  Google Scholar 

  64. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002;165(2):277–304.

    Article  Google Scholar 

  65. Malmberg P, Rask-Andersen A, Rosenhall L. Exposure to microorganisms associated with allergic alveolitis and febrile reactions to mold dust in farmers. Chest. 1993;103(4):1202–9.

    Article  CAS  PubMed  Google Scholar 

  66. Zeiss CR, Kanellakes TM, Bellone JD, Levitz D, Pruzansky JJ, Patterson R. Immunoglobulin E-mediated asthma and hypersensitivity pneumonitis with precipitating anti-hapten antibodies due to diphenylmethane diisocyanate (MDI) exposure. J Allergy Clin Immunol. 1980;65(5):347–52.

    Article  CAS  PubMed  Google Scholar 

  67. Hashisako M, Fukuoka J. Pathology of idiopathic interstitial pneumonias. Clin Med Insights Circ Respir Pulm Med. 2015;9(Suppl 1):123–33.

    PubMed  Google Scholar 

  68. Flaherty KR, Martinez FJ, Travis W, Lynch JP 3rd. Nonspecific interstitial pneumonia (NSIP). Semin Respir Crit Care Med. 2001;22(4):423–34.

    Article  CAS  PubMed  Google Scholar 

  69. Schwaiblmair M. Drug induced interstitial lung disease. Open Respir Med J. 2012;6:63–74.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kaarteenaho R, Kinnula VL. Diffuse alveolar damage: a common phenomenon in progressive interstitial lung disorders. Pulm Med. 2011;2011:1.

    Article  Google Scholar 

  71. Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011;6:147–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Spira D, Wirths S, Skowronski F, Pintoffl J, Kaufmann S, Brodoefel H, et al. Diffuse alveolar hemorrhage in patients with hematological malignancies: HRCT patterns of pulmonary involvement and disease course. Clin Imaging. 2013;37(4):680–6.

    Article  PubMed  Google Scholar 

  73. Kao KC, Hu HC, Chang CH, Hung CY, Chiu LC, Li SH, et al. Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy. Crit Care. 2015;19:228.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Goodman LR. Congestive heart failure and adult respiratory distress syndrome. New insights using computed tomography. Radiol Clin N Am. 1996;34(1):33–46.

    CAS  PubMed  Google Scholar 

  75. Gattinoni L, Presenti A, Torresin A, Baglioni S, Rivolta M, Rossi F, et al. Adult respiratory distress syndrome profiles by computed tomography. J Thorac Imaging. 1986;1(3):25–30.

    Article  CAS  PubMed  Google Scholar 

  76. Pelosi P, Crotti S, Brazzi L, Gattinoni L. Computed tomography in adult respiratory distress syndrome: what has it taught us? Eur Respir J. 1996;9(5):1055–62.

    Article  CAS  PubMed  Google Scholar 

  77. Rogers S. Spencer’s pathology of the lung. Histopathology. 1999;34(5):470.

    Article  CAS  PubMed  Google Scholar 

  78. Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016;54:139–48.

    Article  CAS  PubMed  Google Scholar 

  80. Claessens YE, Debray MP, Tubach F, Brun AL, Rammaert B, Hausfater P, et al. Early chest computed tomography scan to assist diagnosis and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care Med. 2015;192(8):974–82.

    Article  PubMed  Google Scholar 

  81. Hammond E, Sloan C, Newell JD Jr, Sieren JP, Saylor M, Vidal C, et al. Comparison of low- and ultralow-dose computed tomography protocols for quantitative lung and airway assessment. Med Phys. 2017;44(9):4747–57.

    Article  PubMed  Google Scholar 

  82. Franzen D, Schad K, Kowalski B, Clarenbach CF, Stupp R, Dummer R, et al. Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study. Cancer Immunol Immunother. 2018;67(1):127–34.

    Article  CAS  PubMed  Google Scholar 

  83. Raghu G, Mageto YN, Lockhart D, Schmidt RA, Wood DE, Godwin JD. The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: a prospective study. Chest. 1999;116(5):1168–74.

    Article  CAS  PubMed  Google Scholar 

  84. Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncol. 2016;2(12):1607–16.

    Article  PubMed  Google Scholar 

  85. Khunger M, Rakshit S, Pasupuleti V, Hernandez AV, Mazzone P, Stevenson J, et al. Incidence of pneumonitis with use of programmed death 1 and programmed death-ligand 1 inhibitors in non-small cell lung Cancer: a systematic review and meta-analysis of trials. Chest. 2017;152(2):271–81.

    Article  PubMed  Google Scholar 

  86. Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, et al. Pneumonitis in patients treated with anti–programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709–17.

    Article  CAS  PubMed  Google Scholar 

  87. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.

    Article  CAS  PubMed  Google Scholar 

  88. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung Cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  CAS  PubMed  Google Scholar 

  89. Nishino M, Hatabu H, Hodi FS, Ramaiya NH. Drug-related pneumonitis in the era of precision Cancer therapy. JCO Precision Oncol. 2017;1:1–12.

    Google Scholar 

  90. Shohdy KS, Abdel-Rahman O. Risk of pneumonitis with different immune checkpoint inhibitors in NSCLC. Ann Transl Med. 2017;5(17):365.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Fujii T, Colen RR, Bilen MA, Hess KR, Hajjar J, Suarez-Almazor ME, et al. Incidence of immune-related adverse events and its association with treatment outcomes: the MD Anderson Cancer Center experience. Investig New Drugs. 2018;36(4):638–46.

    Article  CAS  Google Scholar 

  92. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Tirumani SH, Ramaiya NH, Keraliya A, Bailey ND, Ott PA, Hodi FS, et al. Radiographic profiling of immune-related adverse events in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res. 2015;3(10):1185–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.

    Article  CAS  PubMed  Google Scholar 

  95. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Khoja L, Day D, Wei-Wu Chen T, Siu LL, Hansen AR. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol. 2017;28(10):2377–85.

    Article  CAS  PubMed  Google Scholar 

  97. Ryu JH, Colby TV, Hartman TE, Vassallo R. Smoking-related interstitial lung diseases: a concise review. Eur Respir J. 2001;17(1):122–32.

    Article  CAS  PubMed  Google Scholar 

  98. Wu J, Hong D, Zhang X, Lu X, Miao J. PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis. Sci Rep. 2017;7:44173.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.

    Article  CAS  PubMed  Google Scholar 

  100. Cui P, Liu Z, Wang G, Ma J, Qian Y, Zhang F, et al. Risk factors for pneumonitis in patients treated with anti-programmed death-1 therapy: a case-control study. Cancer Med. 2018;7:4115.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ribas A, Shin DS, Zaretsky J, Frederiksen J, Cornish A, Avramis E, et al. PD-1 blockade expands intratumoral memory T cells. Cancer Immunol Res. 2016;4(3):194–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Bowyer S, Prithviraj P, Lorigan P, Larkin J, McArthur G, Atkinson V, et al. Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. Br J Cancer. 2016;114(10):1084–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Balagani A, Arain M, Sheshadri A. Bronchiolitis obliterans after combination immunotherapy with pembrolizumab and ipilimumab. J Immunother Precision Oncol. 2018;1(1):49–52.

    Google Scholar 

  105. Kolla BC, Patel MR. Recurrent pleural effusions and cardiac tamponade as possible manifestations of pseudoprogression associated with nivolumab therapy—a report of two cases. J Immunother Cancer. 2016;4:80.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Berthod G, Lazor R, Letovanec I, Romano E, Noirez L, Mazza Stalder J, et al. Pulmonary sarcoid-like granulomatosis induced by ipilimumab. J Clin Oncol. 2012;30(17):e156–9.

    Article  PubMed  Google Scholar 

  108. Bronstein Y, Ng CS, Hwu P, Hwu WJ. Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy. AJR Am J Roentgenol. 2011;197(6):W992–w1000.

    Article  PubMed  Google Scholar 

  109. Reuss JE, Kunk PR, Stowman AM, Gru AA, Slingluff CL Jr, Gaughan EM. Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature. J Immunother Cancer. 2016;4:94.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Tetzlaff MT, Nelson KC, Diab A, Staerkel GA, Nagarajan P, Torres-Cabala CA, et al. Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients. J Immunother Cancer. 2018;6(1):14.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ramstein J, Broos CE, Simpson LJ, Ansel KM, Sun SA, Ho ME, et al. IFN-gamma-producing T-helper 17.1 cells are increased in sarcoidosis and are more prevalent than T-helper type 1 cells. Am J Respir Crit Care Med. 2016;193(11):1281–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Facco M, Cabrelle A, Teramo A, Olivieri V, Gnoato M, Teolato S, et al. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax. 2011;66(2):144–50.

    Article  PubMed  Google Scholar 

  113. von Euw E, Chodon T, Attar N, Jalil J, Koya RC, Comin-Anduix B, et al. CTLA4 blockade increases Th17 cells in patients with metastatic melanoma. J Transl Med. 2009;7:35.

    Article  CAS  Google Scholar 

  114. Attia P, Phan GQ, Maker AV, Robinson MR, Quezado MM, Yang JC, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol. 2005;23(25):6043–53.

    Article  CAS  PubMed  Google Scholar 

  115. Horvat TZ, Adel NG, Dang TO, Momtaz P, Postow MA, Callahan MK, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol. 2015;33(28):3193–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Santini FC, Rizvi H, Wilkins O, van Voorthuysen M, Panora E, Halpenny D, et al. Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy. J Clin Oncol. 2017;35:9012.

    Article  Google Scholar 

  117. Pollack MH, Betof A, Dearden H, Rapazzo K, Valentine I, Brohl AS, et al. Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma. Ann Oncol. 2018;29(1):250–5.

    Article  CAS  PubMed  Google Scholar 

  118. Puzanov I, Diab A, Abdallah K, Bingham CO 3rd, Brogdon C, Dadu R, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Cunliffe A, Armato SG 3rd, Castillo R, Pham N, Guerrero T, Al-Hallaq HA. Lung texture in serial thoracic computed tomography scans: correlation of radiomics-based features with radiation therapy dose and radiation pneumonitis development. Int J Radiat Oncol Biol Phys. 2015;91(5):1048–56.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Colen RR, Fujii T, Bilen MA, Kotrotsou A, Abrol S, Hess KR, et al. Radiomics to predict immunotherapy-induced pneumonitis: proof of concept. Invest New Drugs. 2018;36(4):601–7.

    Article  CAS  PubMed  Google Scholar 

  121. Abraham C, Cho J. Interleukin-23/Th17 pathways and inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(7):1090–100.

    Article  PubMed  Google Scholar 

  122. Tarhini AA, Zahoor H, Lin Y, Malhotra U, Sander C, Butterfield LH, et al. Baseline circulating IL-17 predicts toxicity while TGF-beta1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. J Immunother Cancer. 2015;3:39.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Kim S, Shannon V, Sheshadri A, Kantarjian HM, Garcia-Manero G, Im J, et al. Th1/Th17 hybrid CD4+ cells in bronchial alveolar lavage fluid from leukemia patients with checkpoint inhibitor-induced pneumonitis. J Clin Oncol. 2017;36(5 suppl):204.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Akash Jain, Vickie R. Shannon & Ajay Sheshadri

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  1. Akash Jain
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  2. Vickie R. Shannon
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  3. Ajay Sheshadri
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Correspondence to Ajay Sheshadri .

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  1. MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Aung Naing

  2. Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Joud Hajjar

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Jain, A., Shannon, V.R., Sheshadri, A. (2018). Immune-Related Adverse Events: Pneumonitis. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 995. Springer, Cham. https://doi.org/10.1007/978-3-030-02505-2_6

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