Pembrolizumab for anaplastic thyroid cancer: a case study

Abstract

Blockade of the PD-1/PD-L1 pathway with targeted monoclonal antibodies has demonstrated encouraging anti-tumour activity in multiple cancer types. We present the case of a patient with BRAF-negative stage IVC anaplastic thyroid cancer (ATC) treated with the anti-PD-1 monoclonal antibody, pembrolizumab, following radiographic progression on chemoradiation. Blood samples were collected prior to and at four time points during treatment with pembrolizumab. Mass cytometry was used to determine expression of relevant biomarkers by peripheral blood mononuclear cells. Faecal samples were collected at baseline and 4 weeks following treatment initiation; taxonomic profiling using 16S ribosomal RNA (rRNA) gene sequencing was performed. Following treatment, a marked expansion in CD20+ B cell, CD16+ CD56lo NK cell and CD45RO+ CCR7+ central memory CD4+ T-cell populations was observed in the peripheral blood. Proportions of cells expressing the co-receptors TIGIT, OX40 and CD86 also increased during treatment. A high abundance of bacteria of the order Bacteroidales, specifically from the Bacteroidaceae and Rikenellaceae families, was identified in the faecal microbiota. Moreover, the patient’s microbiome was enriched in Clostridiales order members Ruminococcaceae, Veillonellaceae and Lachnospiraceae. Alpha diversity of the gut microbiome was significantly higher following initiation of checkpoint therapy as assessed by the Shannon and Simpson index. Our results suggest that treatment with pembrolizumab promotes expansion of T-, B- and NK cell populations in the peripheral blood at the time of tumour regression and have the potential to be implemented as predictive biomarkers in the context of checkpoint blockade therapy. Larger studies to confirm these findings are warranted.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Abbreviations

AJCC:

American Joint Committee on Cancer

ATC:

Anaplastic thyroid cancer

BBB:

Blood–brain barrier

Bregs:

Regulatory B cells

CNS:

Central nervous system

CONCERT:

Centre for Oncology Education and Research Translation

CT:

Computed tomography

CTC:

Circulating tumour cells

EBRT:

External beam radiation therapy

FDG:

Fluorodeoxyglucose

FNA:

Fine needle aspiration

HL:

Hodgkin’s lymphoma

IMRT:

Intensity-modulated radiation therapy

irAEs:

Immune-related adverse events

MMT:

Multimodal therapy

NLR:

Neutrophil:lymphocyte ratio

pDCs:

Plasmacytoid dendritic cells

PET/CT:

Positron emission tomography/computed tomography

RCC:

Renal cell carcinoma

sOTUs:

Individual sequence variants

Tfh:

Follicular T-helper cells

TPS:

Tumour proportion score

WBRT:

Whole-brain radiation therapy

References

  1. 1.

    Taccaliti A, Silvetti F, Palmonella G, Boscaro M (2012) Anaplastic thyroid carcinoma. Front Endocrinol 3:84

    Google Scholar 

  2. 2.

    Cornett WR, Sharma AK, Day TA, Richardson MS, Hoda RS, van Heerden JA et al (2007) Anaplastic thyroid carcinoma: an overview. Curr Oncol Rep 9(2):152–158

    PubMed  Google Scholar 

  3. 3.

    Nagaiah G, Hossain A, Mooney CJ, Parmentier J, Remick SC (2011) Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment. J Oncol 2011:542358

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Denaro N, Nigro CL, Russi EG, Merlano MC (2013) The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer. Oncol Targets Therp 9:1231–1241

    Google Scholar 

  5. 5.

    Ayaz T, Sahin SB, Sahin OZ, Akdogan R, Gücer R (2015) Anaplastic thyroid carcinoma presenting with gastric metastasis: a case report. Hippokratia. 19(1):85–87

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Besic N, Gazic B (2013) Sites of metastases of anaplastic thyroid carcinoma: autopsy findings in 45 cases from a single institution. Thyroid 23(6):709–713

    PubMed  Google Scholar 

  7. 7.

    Stavas MJ, Shinohara ET, Attia A, Ning MS, Friedman JM, Cmelak AJ (2014) Short course high dose radiotherapy in the treatment of anaplastic thyroid carcinoma. J Thyroid Res 2014:764281

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Rao SN, Zafereo M, Dadu R, Busaidy NL, Hess K, Cote GJ et al (2017) Patterns of treatment failure in anaplastic thyroid carcinoma. Thyroid 27(5):672–681

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Prasongsook N, Kumar A, Chintakuntlawar AV, Foote RL, Kasperbauer J, Molina J et al (2017) Survival in response to multimodal therapy in anaplastic thyroid cancer. J Clin Endocrinol Metab 102(12):4506–4514

    PubMed  Google Scholar 

  10. 10.

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

    CAS  PubMed  Google Scholar 

  11. 11.

    Bardhan K, Anagnostou T, Boussiotis VA (2016) The PD1:PD-L1/2 pathway from discovery to clinical implementation. Front Immunol 7:550

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF et al (2012) Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Borcherding N, Kolb R, Gullicksrud J, Vikas P, Zhu Y, Zhang W (2018) Keeping tumors in check: a mechanistic review of clinical response and resistance to immune checkpoint blockade in cancer. J Mol Biol 430(14):2014–2029

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Iyer PC, Dadu R, Gule-Monroe M, Busaidy NL, Ferrarotto R, Habra MA et al (2018) Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma. J Immunotherap Cancer 6(1):68

    Google Scholar 

  15. 15.

    Kollipara R, Schneider B, Radovich M, Babu S, Kiel PJ (2017) Exceptional response with immunotherapy in a patient with Anaplastic Thyroid Cancer. Oncologist 22(10):1149–1151. https://doi.org/10.1634/theoncologist.2017-0096

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Wirth LJ, Eigendorff E, Capdevila J, Paz-Ares LG, Lin C-C, Taylor MH et al (2018) Phase I/II study of spartalizumab (PDR001), an anti-PD1 mAb, in patients with anaplastic thyroid cancer. J Clin Oncol 36(15_suppl):6024

    Google Scholar 

  17. 17.

    Chintakuntlawar A, Yin J, Foote RL, Kasperbauer JL, Rivera M, Asmus E, Garces N, Janus J, Ma DJ, Moore EJ, Morris J, Neben-Wittich M, Price D, Ryder M, Van Abel K, Hilger CR, Samb E, Bible K (2018) A phase 2 study of pembrolizumab combined with chemoradiotherapy as initial treatment for anaplastic thyroid cancer. In: 88th Annual Meeting of the American Thyroid Association Washington, DC

  18. 18.

    Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M et al (2017) Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: 2-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol 35(35):3924–3933

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1803–1813

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330

    CAS  Google Scholar 

  21. 21.

    Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Maleki Vareki S, Garrigos C, Duran I (2017) Biomarkers of response to PD-1/PD-L1 inhibition. Crit Rev Oncol Hematol 116:116–124

    PubMed  Google Scholar 

  23. 23.

    McGuire HM, Shklovskaya E, Edwards J, Trevillian PR, McCaughan GW, Bertolino P et al (2018) Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report. Cancer Immunol Immunotherap CII 67(4):563–573

    CAS  Google Scholar 

  24. 24.

    Imrit K, Goldfischer M, Wang J, Green J, Levine J, Lombardo J et al (2006) Identification of bacteria in formalin-fixed, paraffin-embedded heart valve tissue via 16S rRNA gene nucleotide sequencing. J Clin Microbiol 44(7):2609–2611

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Handl S, Dowd SE, Garcia-Mazcorro JF, Steiner JM, Suchodolski JS (2011) Massive parallel 16S rRNA gene pyrosequencing reveals highly diverse fecal bacterial and fungal communities in healthy dogs and cats. FEMS Microbiol Ecol 76(2):301–310

    CAS  PubMed  Google Scholar 

  26. 26.

    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK et al (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP (2016) DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods 13(7):581–583

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Bokulich NA, Kaehler BD, Rideout JR, Dillon M, Bolyen E, Knight R et al (2018) Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2′s q2-feature-classifier plugin. Microbiome 6(1):90

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, Vanderplas J (2011) Scikit-learn: machine learning in Python. J Mach Learn Res 12:2825–2830

    Google Scholar 

  30. 30.

    McDonald D, Price MN, Goodrich J, Nawrocki EP, DeSantis TZ, Probst A et al (2012) An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J 6(3):610–618

    CAS  PubMed  Google Scholar 

  31. 31.

    Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 134(10):2403–2413

    CAS  PubMed  Google Scholar 

  32. 32.

    Paramanathan A, Saxena A, Morris DL (2014) A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol 23(1):31–39

    PubMed  Google Scholar 

  33. 33.

    Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124

    PubMed  Google Scholar 

  34. 34.

    Ding PN, Roberts TL, Chua W, Becker TM, Descallar J, Yip PY et al (2017) Clinical outcomes in patients with advanced epidermal growth factor receptor-mutated non-small-cell lung cancer in South Western Sydney Local Health District. Int Med J 47(12):1405–1411

    CAS  Google Scholar 

  35. 35.

    Sacdalan DB, Lucero JA, Sacdalan DL (2018) Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. OncoTargets Therap 11:955–965

    Google Scholar 

  36. 36.

    Tan Q, Liu S, Liang C, Han X, Shi Y (2018) Pretreatment hematological markers predict clinical outcome in cancer patients receiving immune checkpoint inhibitors: a meta-analysis. Thoracic Cancer. 9(10):1220–1230

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Cowey CL, Liu FX, Black-Shinn J, Stevinson K, Boyd M, Frytak JR et al (2018) Pembrolizumab utilization and outcomes for advanced melanoma in US community oncology practices. J Immunotherap (Hagerstown MD 1997) 41(2):86–95

    CAS  Google Scholar 

  38. 38.

    Dang TO, Ogunniyi A, Barbee MS, Drilon A (2016) Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Expert Rev Anticancer Ther 16(1):13–20

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Fonkem E, Uhlmann EJ, Floyd SR, Mahadevan A, Kasper E, Eton O et al (2012) Melanoma brain metastasis: overview of current management and emerging targeted therapies. Expert Rev Neurother 12(10):1207–1215

    CAS  PubMed  Google Scholar 

  40. 40.

    Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD (2013) Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med 2(6):899–906

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Tallet AV, Dhermain F, Le Rhun E, Noël G, Kirova YM (2017) Combined irradiation and targeted therapy or immune checkpoint blockade in brain metastases: toxicities and efficacy. Ann Oncol 28(12):2962–2976

    CAS  PubMed  Google Scholar 

  42. 42.

    Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP et al (2018) Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 19(5):672–681

    CAS  PubMed  Google Scholar 

  43. 43.

    Arbour KC, Mezquita L, Long N, Rizvi H, Auclin E, Ni A et al (2018) Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small-cell lung cancer. J Clin Oncol 36(28):2872–2878

    CAS  PubMed  Google Scholar 

  44. 44.

    Krieg C, Nowicka M, Guglietta S, Schindler S, Hartmann FJ, Weber LM et al (2018) High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat Med 24:144

    CAS  PubMed  Google Scholar 

  45. 45.

    Lomax AJ, McGuire HM, McNeil C, Choi CJ, Hersey P, Karikios D et al (2017) Immunotherapy-induced sarcoidosis in patients with melanoma treated with PD-1 checkpoint inhibitors: case series and immunophenotypic analysis. Int J Rheumatic Dis 20(9):1277–1285

    CAS  Google Scholar 

  46. 46.

    Kamphorst AO, Pillai RN, Yang S, Nasti TH, Akondy RS, Wieland A et al (2017) Proliferation of PD-1 + CD8 T cells in peripheral blood after PD-1–targeted therapy in lung cancer patients. Proc Natl Acad Sci 114(19):4993–4998

    CAS  PubMed  Google Scholar 

  47. 47.

    Yuseff MI, Pierobon P, Reversat A, Lennon-Dumenil AM (2013) How B cells capture, process and present antigens: a crucial role for cell polarity. Nat Rev Immunol 13(7):475–486

    CAS  PubMed  Google Scholar 

  48. 48.

    Guy TV, Terry AM, Bolton HA, Hancock DG, Shklovskaya E, de Fazekas SGB (2016) Pro- and anti-tumour effects of B cells and antibodies in cancer: a comparison of clinical studies and preclinical models. Cancer Immunol Immunotherap 65(8):885–896

    CAS  Google Scholar 

  49. 49.

    Varn FS, Wang Y, Cheng C (2019) A B cell-derived gene expression signature associates with an immunologically active tumor microenvironment and response to immune checkpoint blockade therapy. Oncoimmunology 8(1):e1513440

    PubMed  Google Scholar 

  50. 50.

    Sarvaria A, Madrigal JA, Saudemont A (2017) B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol 14(8):662–674

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Grossenbacher SK, Aguilar EG, Murphy WJ (2017) Leveraging natural killer cells for cancer immunotherapy. Immunotherapy 9(6):487–497

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet (Lond Engl) 356(9244):1795–1799

    CAS  Google Scholar 

  53. 53.

    Kim HS (2015) A multifaceted approach targeting NK cells for better treatment of cancer: focus on hematological malignancies. Blood Res 50(4):189–191

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J et al (2016) Programmed death-1 blockade with pembrolizumab in patients with classical hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol 34(31):3733–3739

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Tallerico R, Cristiani CM, Staaf E, Garofalo C, Sottile R, Capone M et al (2017) IL-15, TIM-3 and NK cells subsets predict responsiveness to anti-CTLA-4 treatment in melanoma patients. Oncoimmunology 6(2):e1261242

    PubMed  Google Scholar 

  56. 56.

    Labidi-Galy SI, Treilleux I, Goddard-Leon S, Combes JD, Blay JY, Ray-Coquard I et al (2012) Plasmacytoid dendritic cells infiltrating ovarian cancer are associated with poor prognosis. Oncoimmunology 1(3):380–382

    PubMed  PubMed Central  Google Scholar 

  57. 57.

    Jensen TO, Schmidt H, Moller HJ, Donskov F, Hoyer M, Sjoegren P et al (2012) Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma. Cancer 118(9):2476–2485

    CAS  PubMed  Google Scholar 

  58. 58.

    Treilleux I, Blay JY, Bendriss-Vermare N, Ray-Coquard I, Bachelot T, Guastalla JP et al (2004) Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res 10(22):7466–7474

    CAS  PubMed  Google Scholar 

  59. 59.

    Pinto A, Rega A, Crother TR, Sorrentino R (2012) Plasmacytoid dendritic cells and their therapeutic activity in cancer. Oncoimmunology. 1(5):726–734

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Lai Y-P, Jeng C-J, Chen S-C (2011) The roles of CD4 + T cells in tumor immunity. ISRN Immunol 2011:6

    Google Scholar 

  61. 61.

    Takeuchi Y, Tanemura A, Tada Y, Katayama I, Kumanogoh A, Nishikawa H (2018) Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4 + T cells in patients with malignant melanoma. Int Immunol 30(1):13–22

    CAS  PubMed  Google Scholar 

  62. 62.

    Tarhini AA, Edington H, Butterfield LH, Lin Y, Shuai Y, Tawbi H et al (2014) Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. PLoS One 9(2):e87705

    PubMed  PubMed Central  Google Scholar 

  63. 63.

    Spitzer MH, Carmi Y, Reticker-Flynn NE, Kwek SS, Madhireddy D, Martins MM et al (2017) Systemic immunity is required for effective cancer immunotherapy. Cell 168(3):487–502.e15

    PubMed  PubMed Central  Google Scholar 

  64. 64.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Toor SM, Syed Khaja AS, Alkurd I, Elkord E (2018) In-vitro effect of pembrolizumab on different T regulatory cell subsets. Clin Exp Immunol 191(2):189–197

    CAS  Google Scholar 

  66. 66.

    Lipson EJ, Forde PM, Hammers H-J, Emens LA, Taube JM, Topalian SL (2015) Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol 42(4):587–600

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Ott PA, Hodi FS, Kaufman HL, Wigginton JM, Wolchok JD (2017) Combination immunotherapy: a road map. J Immunother Cancer. 5:16

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    Li K, Qu S, Chen X, Wu Q, Shi M (2017) Promising Targets for Cancer Immunotherapy: TLRS, RLRs, and STING-mediated innate immune pathways. Int J Mol Sci 18(2):404

    PubMed Central  Google Scholar 

  69. 69.

    Kurtulus S, Sakuishi K, Ngiow SF, Joller N, Tan DJ, Teng MW et al (2015) TIGIT predominantly regulates the immune response via regulatory T cells. J Clin Investig 125(11):4053–4062

    Google Scholar 

  70. 70.

    Anderson AC, Joller N, Kuchroo VK (2016) Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 44(5):989–1004

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K et al (2013) OX40 is a potent immune-stimulating target in late-stage cancer patients. Can Res 73(24):7189–7198

    CAS  Google Scholar 

  72. 72.

    Infante JR, Hansen AR, Pishvaian MJ, Chow LQM, McArthur GA, Bauer TM et al (2016) A phase Ib dose escalation study of the OX40 agonist MOXR0916 and the PD-L1 inhibitor atezolizumab in patients with advanced solid tumors. J Clin Oncol 34(15_suppl):101

    Google Scholar 

  73. 73.

    Harris SJ, Brown J, Lopez J, Yap TA (2016) Immuno-oncology combinations: raising the tail of the survival curve. Cancer Biol Med 13(2):171–193

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science (New York, NY). 359(6371):91–97

    CAS  PubMed  Google Scholar 

  76. 76.

    Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP et al (2017) Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia (New York, NY). 19(10):848–855

    CAS  Google Scholar 

  77. 77.

    Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C et al (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science (New York, NY). 350(6264):1079–1084

    PubMed  PubMed Central  Google Scholar 

  78. 78.

    Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV et al (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science (New York, NY). 359(6371):97–103

    CAS  Google Scholar 

  79. 79.

    Derbel O, Limem S, Segura-Ferlay C, Lifante JC, Carrie C, Peix JL et al (2011) Results of combined treatment of anaplastic thyroid carcinoma (ATC). BMC Cancer 11:469

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Seto A, Sugitani I, Toda K, Kawabata K, Takahashi S, Saotome T (2015) Chemotherapy for anaplastic thyroid cancer using docetaxel and cisplatin: report of eight cases. Surg Today 45:221–226

    CAS  PubMed  Google Scholar 

  81. 81.

    Caixeiro NJ, Aghmesheh, M., de Souza P, Lee, CS (2015) The Centre for Oncology Education and Research Translation (CONCERT) Biobank. Open J Bioresour 2(1):Art. e3. doi: http://doi.org/10.5334/ojb.ai

Download references

Funding

This research was funded by the Ingham Institute for Applied Medical Research Circulating Tumour Cells (CTC) Head and Neck Research Grant, Liverpool Hospital and Cancer Council NSW (APP1147099) HM is the recipient of the Early Career Fellowship (GNT1037298).  TLR is the recipient of a Cancer Institute New South Wales Future Research Leader Fellowship and salary support from Cancer Institute NSW (CINSW) translational cancer research centre CONCERT.

Author information

Affiliations

Authors

Contributions

Study conception and design was done by TLR, PS, VB, MJA, AC, HM, NN, BFSG. Experiments were performed and analysed by TLR, MJA, HM, TJ. Clinical data and samples were prepared and interpreted by TLR, AC, MJA, JS, KI. All authors made substantial contributions to data interpretation, manuscript preparation and review.

Corresponding author

Correspondence to Marra Jai Aghajani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and ethical standards

All research was performed under Human Research ethics committee (HREC) protocols from Liverpool Hospital (Project number 13/097, HREC/13/LPOOL/158) (South West Sydney Local Health District), facilitated by the Centre for Oncology Education and Research Translation (CONCERT) Biobank, in accordance with relevant legislation [81].

Informed consent

Written informed consent was obtained from the patient who is the subject of the case study on January 10th, 2018. The patient agreed to the publication of this case study and the use of their specimens (provided that the participant could not be identified). Written informed consent was obtained from all controls prior to the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 676 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Aghajani, M.J., Cooper, A., McGuire, H. et al. Pembrolizumab for anaplastic thyroid cancer: a case study. Cancer Immunol Immunother 68, 1921–1934 (2019). https://doi.org/10.1007/s00262-019-02416-7

Download citation

Keywords

  • Anti-PD-1 antibody
  • Pembrolizumab
  • Checkpoint inhibitor
  • Anaplastic thyroid cancer (ATC)