Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer

Journal of Clinical Endocrinology and Metabolism

Volumn 101, Issue 7, 2016, Pages 2863-2873

  Bastman, Jill J ^a   Serracino, Hilary S ^a   Zhu, Yuwen ^b   Koenig, Michelle R ^b   Mateescu, Valerica ^a   Sams, Sharon B ^a   Davies, Kurtis D ^a   Raeburn, Christopher D ^b   McIntyre, Robert C ^b   Haugen, Bryan R ^a,c   French, Jena D ^a,c  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEVACIZUMAB; CD3 ANTIGEN; CD8 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; IMMUNE CHECKPOINT PROTEIN; PAZOPANIB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 2; PROGRAMMED DEATH 1 RECEPTOR; RNA 18S; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN; PDCD1 PROTEIN, HUMAN; TUMOR MARKER;

ACUTE T-CELL LEUKEMIA CELL LINE; ADULT; ADVANCED CANCER; ANAPLASTIC THYROID CARCINOMA; ARTICLE; AUTOIMMUNE THYROIDITIS; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER PROGNOSIS; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL INFILTRATION; CYTOKINE PRODUCTION; DIFFERENTIATED THYROID CANCER; DISEASE SEVERITY; DISTANT METASTASIS; FEMALE; FINE NEEDLE ASPIRATION BIOPSY; FLOW CYTOMETRY; GENE EXPRESSION; GENE FREQUENCY; GENE MUTATION; GENE OVEREXPRESSION; HISTOLOGY; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; LYMPH NODE METASTASIS; LYMPHOCYTIC INFILTRATION; MAJOR CLINICAL STUDY; MALE; NECK DISSECTION; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY T LYMPHOCYTE; RNA ISOLATION; SIGNAL TRANSDUCTION; STERNUM; T LYMPHOCYTE; THYROID CANCER CELL LINE; THYROID FOLLICULAR CARCINOMA; THYROID PAPILLARY CARCINOMA; THYROID PARAFOLLICULAR CELL; THYROIDECTOMY; TUMOR ASSOCIATED LEUKOCYTE; TUMOR BIOPSY; TUMOR MICROENVIRONMENT; TUMOR VOLUME; AGED; CELL CYCLE CHECKPOINT; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; MIDDLE AGED; PATHOLOGY; PHYSIOLOGY; PROGNOSIS; THYROID CARCINOMA, ANAPLASTIC; THYROID NEOPLASMS; TUMOR INVASION;

ADULT; AGED; BIOMARKERS, TUMOR; CD8-POSITIVE T-LYMPHOCYTES; CELL CYCLE CHECKPOINTS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MIDDLE AGED; NEOPLASM INVASIVENESS; PROGNOSIS; PROGRAMMED CELL DEATH 1 RECEPTOR; SIGNAL TRANSDUCTION; THYROID CARCINOMA, ANAPLASTIC; THYROID NEOPLASMS;

EID: 85013254723     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/JC.2015-4227     Document Type: Article

References (67)

1. Howlader N, Noone AM, Krapcho M, et al, eds. Surveillance Epidemiology and End Results (SEER): cancer statistics review, 1975–2008. National Cancer Institute (Bethesda, MD). Based on November 2010 SEER data submission, posted to the SEER web site, 2011, http://seer.cancer.gov/csr/1975_2008.
2. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015; 372:621– 630.
3. French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR. Tumor-associated lymphocytes and increased FoxP3 regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. J Clin Endocrinol Metab. 2010;95:2325–2333.
4. Gogali F, Paterakis G, Rassidakis GZ, et al. Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid. J Clin Endocrinol Metab. 2012;97:1474 –1482.
5. French JD, Kotnis GR, Said S, et al. Programmed death-1 T cells and regulatory T cells are enriched in tumor-involved lymph nodes and associated with aggressive features in papillary thyroid cancer. J Clin Endocrinol Metab. 2012;97:E934 –E943.
6. Severson JJ, Serracino HS, Mateescu V, et al. PD-1Tim-3 CD8 T lymphocytes display varied degrees of functional exhaustion in patients with regionally metastatic differentiated thyroid cancer. Cancer Immunol Res. 2015;3:620 – 630.
7. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492– 499.
8. Wherry EJ, Ha SJ, Kaech SM, et al. Molecular signature of CD8 T cell exhaustion during chronic viral infection. Immunity. 2007; 27:670–684.
9. Ahmadzadeh M, Johnson LA, Heemskerk B, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114:1537–1544.
10. Baitsch L, Baumgaertne, P, Devevre E, et al. Exhaustion of tumor-specific CD8() T cells in metastases from melanoma patients. J Clin Invest. 2011;121:2350 –2360.
11. Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8 T cell dysfunction in melanoma patients. J Exp Med. 2010;207:2175–2186.
12. Riches, JC, Davies, JK, McClanahan, F, et al. T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production. Blood. 2013;121:1612–1621.
13. Zippelius A, Batard P, Rubio-Godoy V, et al. Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Cancer Res. 2004;64:2865–2873.
14. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
15. Hino R, Kabashima K, Kato Y, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116:1757–1766.
16. Thompson RH, Kuntz SM, Leibovich BC, et al. Tumor B7–H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66:3381–3385.
17. Karim R, Jordanova ES, Piersma SJ, et al. Tumor-expressed B7–H1 and B7-DC in relation to PD-1 T-cell infiltration and survival of patients with cervical carcinoma. Clin Cancer Res. 2009;15:6341–6347.
18. Ohigashi Y, Sho M, Yamada Y, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 2005;11: 2947–2953.
19. Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20: 5064 –5074.
20. Batistatou A, Zolota V, Scopa CD. S-100 protein dendritic cells and CD34 dendritic interstitial cells in thyroid lesions. Endocr Pathol. 2002;13:111–115.
21. Caillou B, Talbot M, Weyemi U, et al. Tumor-associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma. PLoS One. 2011;6:e22567.
22. Qing W, Fang WY, Ye L, et al. Density of tumor-associated macrophages correlates with lymph node metastasis in papillary thyroid carcinoma. Thyroid. 2012;22:905–910.
23. Ryder M, Ghossein RA, Ricarte-Filho JC, Knauf JA, Fagin JA. Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer. Endocr Relat Cancer. 2008;15:1069 –1074.
24. Scarpino S, Stoppacciaro A, Ballerini F, et al. Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells. Am J Pathol. 2000;156:831– 837.
25. Green FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M, eds. AJCC Cancer Staging Handbook: TNM Classification of Malignant Tumors. 6th ed. New York: Springer; 2002.
26. Kleinschmidt-DeMasters BK, Aisner DL, Birks DK, Foreman NK. Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol. 2013;37:685– 698.
27. Phillips T, Murray G, Wakamiya K, et al. Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. Appl Immunohistochem Mol Morphol. 2007;15:325–331.
28. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13:184 –199.
29. Mesa C Jr, Mirza M, Mitsutake N, et al. Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling. Cancer Res. 2006;66:6521– 6529.
30. Angell TE, Lechner MG, Jang JK, Correa AJ, LoPresti JS, Epstein AL. BRAF V600E in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration. Thyroid. 2014;24:1385–1393.
31. Khalili JS, Liu S, Rodriguez-Cruz TG, et al. Oncogenic BRAF(V600E) promotes stromal cell-mediated immunosuppression via induction of interleukin-1 in melanoma. Clin Cancer Res. 2012;18:5329 –5340.
32. Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–3175.
33. Brahmer, JR, Tykodi, SS, Chow, LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455–2465.
34. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369: 134 –144.
35. Rizvi NA, Mazieres J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015; 16:257–265.
36. Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1treatmentwithpembrolizumabinipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109–1117.
37. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–2454.
38. Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515:568–571.
39. Cunha LL, Marcello MA, Morari EC, et al. Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation. Endocr Relat Cancer. 2013;20:103–110.
40. Amarnath S, Mangus CW, Wang JC, et al. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med. 2011;3:111ra120.
41. Duraiswamy J, Freeman GJ, Coukos G. Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer. Cancer Res. 2013;73:6900 – 6912.
42. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015–3029.
43. Kitazawa Y, Fujino M, Wang Q, et al. Involvement of the programmed death-1/programmed death-1 ligand pathway in CD4CD25 regulatory T-cell activity to suppress alloimmune responses. Transplantation. 2007;83:774–782.
44. Ugolini C, Basolo F, Proietti A, et al. Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly differentiated, and undifferentiated thyroid carcinoma. Thyroid. 2007;17:389–393.
45. Ryder M, Callahan M, Postow MA, Wolchok J, Fagin JA. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer. 2014;21:371–381.
46. Hou P, Liu D, Shan Y, Hu S, et al. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res. 2007;13:1161–1170.
47. Jiang X, Zhou J, Giobbie-Hurder A, Wargo J, Hodi FS. The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res. 2013;19:598 – 609.
48. Saji M, Ringel MD. The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors. Mol Cell Endocrinol. 2010;321:20 – 28.
49. Boni A, Cogdill AP, Dang P, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 2010;70:5213–5219.
50. Frederick DT, Piris A, Cogdill AP, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013;19:1225–1231.
51. Sapkota B, Hill CE, Pollack BP. Vemurafenib enhances MHC induction in BRAF homozygous melanoma cells. Oncoimmunology. 2013;2:e22890.
52. Bradley SD, Chen Z, Melendez B, et al. BRAFV600E co-opts a conserved MHC class I internalization pathway to diminish antigen presentation and CD8 T-cell recognition of melanoma. Cancer Immunol Res. 2015;3:602– 609.
53. Knight DA, Ngiow SF, Li M, et al. Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Invest. 2013;123: 1371–1381.
54. Liu C, Peng W, Xu C, et al. BRAF inhibition increases tumor infiltration by T cells and enhances the antitumor activity of adoptive immunotherapy in mice. Clin Cancer Res. 2013;19:393– 403.
55. Wilmott JS, Long GV, Howle JR, et al. Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 2012;18:1386 –1394.
56. Brauner E, Gunda V, Vanden Borre PV, et al. Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer. Oncotarget. In press.
57. Vanden Borre P, Gunda V, McFadden DG, et al. Combined BRAF(V600E)- and SRC-inhibition induces apoptosis, evokes an immune response and reduces tumor growth in an immunocompetent orthotopic mouse model of anaplastic thyroid cancer. Oncotarget. 2014;5:3996–4010.
58. Alfaro C, Suarez N, Gonzalez A, et al. Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes. Br J Cancer. 2009;100:1111–1119.
59. Almand B, Resser JR, Lindman B, et al. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res. 2000;6:1755–1766.
60. Dikov MM, Ohm JE, Ray N, et al. Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation. J Immunol. 2005;174:215–222.
61. Gabrilovich D, Ishida T, Oyama T, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood. 1998;92:4150–4166.
62. Voron T, Marcheteau E, Pernot S, et al. Control of the immune response by pro-angiogenic factors. Front Oncol. 2014;4:70.
63. Coffelt SB, Chen YY, Muthana M, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol. 2011;186:4183–4190.
64. Ghiringhelli F, Puig PE, Roux S, et al. Tumor cells convert immature myeloid dendritic cells into TGF-secreting cells inducing CD4CD25 regulatory T cell proliferation. J Exp Med. 2005; 202:919 –929.
65. Huang B, Pan PY, Li Q, et al. Gr-1CD115 immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 2006;66:1123–1131.
66. Terme M, Pernot S, Marcheteau E, et al. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 2013;73:539 –549.
67. Voron T, Colussi O, Marcheteau E, et al. VEGF-A modulates the expression of inhibitory checkpoints on CD8 T cells in tumors. J Exp Med. 2015;212:139 –148.