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Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group

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A Correction to this article was published on 21 October 2020

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Abstract

Programmed death 1 ligand (PD-L1) is an immunomodulatory molecule expressed by cancer cells, and it has been widely demonstrated to inhibit host antitumor responses. The aim of the present study was to identify clinicopathological features associated with PD-L1 expression in the secondary solid cancers of patients after allogeneic hematopoietic stem cell transplantation. In this database of 530 patients who received allo-HSCT between 1990 and 2017, 15 developed solid cancers with a median interval of 3487 days after transplantation. Three patients had 2 different solid cancers. Eighteen solid cancer cases were identified. A multivariate analysis showed that chronic graft-versus-host disease (GVHD) was associated with an increased risk of solid cancer. The presence of chronic GVHD was observed in 8 out of 18 cases at the diagnosis of secondary malignancies. PD-L1 expression levels in cancers were significantly higher in patients with active chronic GVHD than in those without chronic GVHD (P = 0.020). Five cases of cancer that developed in the involved organs of chronic GVHD showed 30% or higher PD-L1 positivity. The present results revealed distinct PD-L1 expression in the secondary solid cancers of post-transplant patients with chronic GVHD.

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  • 21 October 2020

    In the original publication of the article, the authors would like to alter the color of characters in the Supplemental Table 1 and 2.

References

  1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354:1813–26.

    CAS  PubMed  Google Scholar 

  2. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Hahn T, McCarthy PL Jr, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31:2437–49.

    PubMed  PubMed Central  Google Scholar 

  4. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socíe G, Travis LB, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336:897–904.

    CAS  PubMed  Google Scholar 

  5. Bhatia S, Louie AD, Bhatia R, O'Donnell MR, Fung H, Kashyap A, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19:464–71.

    CAS  PubMed  Google Scholar 

  6. Baker KS, DeFor TE, Burns LJ, Ramsay NK, Neglia JP, Robison LL. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol. 2003;21:1352–8.

    PubMed  Google Scholar 

  7. Majhail NS, Brazauskas R, Rizzo JD, Sobecks RM, Wang Z, Horowitz MM, et al. Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood. 2011;117:316–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Rizzo JD, Curtis RE, Socié G, Sobocinski KA, Gilbert E, Landgren O, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood. 2009;113:1175–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Atsuta Y, Suzuki R, Yamashita T, Fukuda T, Miyamura K, Taniguchi S, et al. Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease. Ann Oncol. 2014;25:435–41.

    CAS  PubMed  Google Scholar 

  10. Shimada K, Yokozawa T, Atsuta Y, Kohno A, Maruyama F, Yano K, et al. Solid tumors after hematopoietic stem cell transplantation in Japan: incidence, risk factors and prognosis. Bone Marrow Transplant. 2005;36:115–21.

    CAS  PubMed  Google Scholar 

  11. Yokota A, Ozawa S, Masanori T, Akiyama H, Ohshima K, Kanda Y, et al. Secondary solid tumors after allogeneic hematopoietic SCT in Japan. Bone Marrow Transplant. 2012;47:95–100.

    CAS  PubMed  Google Scholar 

  12. Vajdic CM, Mayson E, Dodds AJ, O'Brien T, Wilcox L, Nivison-Smith I, et al. Second cancer risk and late mortality in adult Australians receiving allogeneic hematopoietic stem cell transplantation: a population-based cohort study. Biol Blood Marrow Transplant. 2016;22:949–56.

    PubMed  Google Scholar 

  13. Atsuta Y, Hirakawa A, Nakasone H, Kurosawa S, Oshima K, Sakai R, et al. Late mortality and causes of death among long-term survivors after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:1702–9.

    PubMed  Google Scholar 

  14. Curtis RE, Metayer C, Rizzo JD, Socié G, Sobocinski KA, Flowers ME, et al. Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood. 2005;105:3802–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Majhail NS. Secondary cancers following allogeneic haematopoietic cell transplantation in adults. Br J Haematol. 2011;154:301–10.

    PubMed  Google Scholar 

  16. Croci DO, Zacarías Fluck MF, Rico MJ, Matar P, Rabinovich GA, Scharovsky OG. Dynamic cross-talk between tumor and immune cells in orchestrating the immunosuppressive network at the tumor microenvironment. Cancer Immunol Immunother. 2007;56:1687–700.

    PubMed  Google Scholar 

  17. Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother. 2007;56:739–45.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99:12293–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–544.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27:450–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Page DB, Postow MA, Callahan MK, Allison JP, Wolchok JD. Immune modulation in cancer with antibodies. Annu Rev Med. 2014;65:185–202.

    CAS  PubMed  Google Scholar 

  24. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311–9.

    PubMed  Google Scholar 

  25. Hughes T, Adler A, Kelly JA, Kaufman KM, Williams AH, Langefeld CD, et al. Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus. Arthritis Rheum. 2012;64:485–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Prokunina L, Castillejo-López C, Oberg F, Gunnarsson I, Berg L, Magnusson V, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002;32:666–9.

    CAS  PubMed  Google Scholar 

  27. Thorburn CM, Prokunina-Olsson L, Sterba KA, Lum RF, Seldin MF, Alarcon-Riquelme ME, et al. Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort. Genes Immun. 2007;8:279–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu JL, Zhang FY, Liang YH, Xiao FL, Zhang SQ, Cheng YL, et al. Association between the PD1.3A/G polymorphism of the PDCD1 gene and systemic lupus erythematosus in European populations: a meta-analysis. J Eur Acad Dermatol Venereol. 2009;23:425–32.

    PubMed  Google Scholar 

  29. Kong EK, Prokunina-Olsson L, Wong WH, Lau CS, Chan TM, Alarcón-Riquelme M, et al. A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese. Arthritis Rheum. 2005;52:1058–62.

    CAS  PubMed  Google Scholar 

  30. Prokunina L, Padyukov L, Bennet A, de Faire U, Wiman B, Prince J, et al. Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum. 2004;50:1770–3.

    CAS  PubMed  Google Scholar 

  31. Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST. Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes. Tissue Antigens. 2003;62:492–7.

    CAS  PubMed  Google Scholar 

  32. Ni R, Ihara K, Miyako K, Kuromaru R, Inuo M, Kohno H, et al. PD-1 gene haplotype is associated with the development of type 1 diabetes mellitus in Japanese children. Hum Genet. 2007;121:223–32.

    CAS  PubMed  Google Scholar 

  33. Juchem KW, Sacirbegovic F, Zhang C, Sharpe AH, Russell K, McNiff JM, et al. PD-L1 prevents the development of autoimmune heart disease in graft-versus-host disease. J Immunol. 2018;200:834–46.

    CAS  PubMed  Google Scholar 

  34. Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A, et al. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood. 2013;122:3062–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 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;373:1627–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–67.

    PubMed  PubMed Central  Google Scholar 

  38. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Fakhry C, Lacchetti C, Rooper LM, Jordan RC, Rischin D, Sturgis EM, et al. Human papillomavirus testing in head and neck carcinomas: ASCO clinical practice guideline endorsement of the college of American Pathologists Guideline. J Clin Oncol. 2018;36(31):3152–61.

    PubMed  Google Scholar 

  40. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  41. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.

    CAS  PubMed  Google Scholar 

  42. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.

    PubMed  PubMed Central  Google Scholar 

  43. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71.

    CAS  PubMed  Google Scholar 

  44. Yokoyama S, Miyoshi H, Nakashima K, Shimono J, Hashiguchi T, Mitsuoka M, et al. Prognostic value of programmed death ligand 1 and programmed death 1 expression in thymic carcinoma. Clin Cancer Res. 2016;22(18):4727–34.

    CAS  PubMed  Google Scholar 

  45. Shimura S, Yang G, Ebara S, Wheeler TM, Frolov A, Thompson TC. Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression. Cancer Res. 2000;60(20):5857–61.

    CAS  PubMed  Google Scholar 

  46. Miyoshi H, Kiyasu J, Kato T, Yoshida N, Shimono J, Yokoyama S, et al. PD-L1 expression on neoplastic or stromal cells is respectively a poor or good prognostic factor for adult t-cell leukemia/lymphoma. Blood. 2016;128(10):1374–81.

    CAS  PubMed  Google Scholar 

  47. Kazama R, Miyoshi H, Takeuchi M, Miyawaki K, Nakashima K, Yoshida N, et al. Combination of CD47 and SIRPα constituting the "Don't Eat Me Signal" is a prognostic factor in diffuse large b-cell lymphoma. Cancer Sci. 2020. https://doi.org/10.1111/cas.14437.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.

    CAS  PubMed  Google Scholar 

  49. Fine JP, Gray RJ. A proportional hazards model for subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Google Scholar 

  50. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    CAS  PubMed  Google Scholar 

  51. Santoiemma PP, Powell DJ Jr. Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther. 2015;16(6):807–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Bremnes RM, Busund LT, Kilvær TL, Andersen S, Richardsen E, Paulsen EE, et al. The role of tumor-infiltrating lymphocytes in development, progression, and prognosis of non-small cell lung cancer. J Thorac Oncol. 2016;11(6):789–800.

    PubMed  Google Scholar 

  53. Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.

    PubMed  Google Scholar 

  54. Harada K, Dong X, Estrella JS, Correa AM, Xu Y, Hofstetter WL, et al. Tumor-associated macrophage infiltration is highly associated with PD-L1 expression in gastric adenocarcinoma. Gastric Cancer. 2018;21:31–40.

    CAS  PubMed  Google Scholar 

  55. Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206(6):1327–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Nagano S, et al. Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers. Nature. 2016;534:402–6.

    CAS  PubMed  Google Scholar 

  57. Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res. 2013;73:1733–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Syrjänen S. Human papillomavirus (HPV) in head and neck cancer. J Clin Virol. 2005;32:S59–S66.

    PubMed  Google Scholar 

  59. Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982–1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:622–35.

    CAS  PubMed  Google Scholar 

  60. Howley PM, Pfister HJ. Beta genus papillomaviruses and skin cancer. Virology. 2015;479–480:290–6.

    PubMed  Google Scholar 

  61. Hufbauer M, Akgül B. Molecular mechanisms of human papillomavirus induced skin carcinogenesis. Viruses. 2017;9(7):187.

    PubMed Central  Google Scholar 

  62. Yang YG, Wang H, Asavaroengchai W, Dey BR. Role of interferon-gamma in GVHD and GVL. Cell Mol Immunol. 2005;2(5):323–9.

    CAS  PubMed  Google Scholar 

  63. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7–h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4:127–37.

    Google Scholar 

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Acknowledgements

The authors thank the many hematologists at Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, for the diagnosis and treatment of post-transplant patients with solid cancers. This work was partly supported by the grant from Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in Aid for Young Scientists (B) (#17K16189) for H.I..

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Authors and Affiliations

  1. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Sachie Kasai, Machiko Fujioka & Yasushi Miyazaki

  2. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4, Sakamoto, Nagasaki city, Nagasaki, Japan

    Hidehiro Itonaga, Tomoko Hata & Yasushi Miyazaki

  3. Department of Pathology, Sasebo City General Hospital, Sasebo, Japan

    Daisuke Niino

  4. Department of Pathology, School of Medicine, Kurume University, Kurume, Japan

    Hiroaki Miyoshi & Koichi Ohshima

  5. Department of Hematology, National Hospital Organization Nagasaki Medical Center, Omura, Japan

    Takeharu Kato & Shinichiro Yoshida

  6. Department of Hematology, Nagasaki Prefecture Gotochuoh Hospital, Goto, Japan

    Daisuke Imanishi

  7. Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan

    Machiko Fujioka, Shinya Sato, Yasushi Sawayama, Yoshitaka Imaizumi & Yasushi Miyazaki

  8. Department of Hematology, Sasebo City General Hospital, Sasebo, Japan

    Takafumi Furumoto & Yukiyoshi Moriuchi

  9. Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan

    Jun Taguchi

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  1. Sachie Kasai
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Contributions

SK, HI, and YM conceived and designed the study; SK, HI, TK, DI, MF, TF, SS, YS, J.T., and YM collected samples and clinical data; SK and DN performed pathological assessments; SK and HI performed statistical analyses; SK, HI, HM, KO, and YM interpreted the data; SK, HI, and YM wrote the manuscript and created the figures and tables; and all the authors critically reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to Hidehiro Itonaga.

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Ethical approval

This study was approved by the Ethics Committees of Nagasaki University Hospital (approval no. 18052108–4), Sasebo City General Hospital (approval no. 2018-A020), the National Hospital Organization Nagasaki Medical Center (approval no. 30034), and Nagasaki Prefecture Gotochuoh Hospital (approval no. 30–4) at which this study was performed.

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Kasai, S., Itonaga, H., Niino, D. et al. Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group. Int J Hematol 112, 524–534 (2020). https://doi.org/10.1007/s12185-020-02926-6

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