PD-1+ and Foxp3+ T cell reduction correlates with survival of HCC patients after sorafenib therapy

JCI Insight

Volumn 1, Issue 11, 2016, Pages

  Kalathil, Suresh Gopi ^a   Lugade, Amit Anand ^a   Miller, Austin ^a   Iyer, Renuka ^a   Thanavala, Yasmin ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85015835253     PISSN: None     EISSN: 23793708     Source Type: Journal    
DOI: 10.1172/jci.insight.86182     Document Type: Article

References (32)

1. Wilhelm S, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5(10):835–844.
2. Voron T, et al. Control of the immune response by pro-angiogenic factors. Front Oncol. 2014;4:70.
3. 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(23):6900–6912.
4. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24(2):207–212.
5. Topalian SL, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–2454.
6. Topalian SL, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020–1030.
7. Hamid O, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134–144.
8. Kalathil S, Lugade AA, Miller A, Iyer R, Thanavala Y. Higher frequencies of GARP(+)CTLA-4(+)Foxp3(+) T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality. Cancer Res. 2013;73(8):2435–2444.
9. Fu J, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132(7):2328–2339.
10. Hoechst B, et al. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+) CD25(+)Foxp3(+) T cells. Gastroenterology. 2008;135(1):234–243.
11. Lugade AA, Kalathil S, Miller A, Iyer R, Thanavala Y. High immunosuppressive burden in advanced hepatocellular carcinoma patients: Can effector functions be restored?. Oncoimmunology. 2013;2(7):e24679.
12. Klein O, et al. Flt3 ligand expands CD4+ FoxP3+ regulatory T cells in human subjects. Eur J Immunol. 2013;43(2):533–539.
13. Lechner MG, et al. Functional characterization of human Cd33+ and Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines. J Transl Med. 2011;9:90.
14. Pan PY, et al. Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood. 2008;111(1):219–228.
15. Chen ML, et al. Sorafenib relieves cell-intrinsic and cell-extrinsic inhibitions of effector T cells in tumor microenvironment to augment antitumor immunity. Int J Cancer. 2014;134(2):319–331.
16. Voron T, et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 2015;212(2):139–148.
17. Caraglia M, et al. Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR. Cell Death Dis. 2011;2:e150.
18. Liu XD, et al. Resistance to Antiangiogenic Therapy Is Associated with an Immunosuppressive Tumor Microenvironment in Metastatic Renal Cell Carcinoma. Cancer Immunol Res. 2015;3(9):1017–1029.
19. Cariani E, et al. Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma. PLoS ONE. 2012;7(3):e32493.
20. Suzuki H, et al. VEGFR2 is selectively expressed by FOXP3high CD4+ Treg. Eur J Immunol. 2010;40(1):197–203.
21. Cao M, et al. Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model. Lab Invest. 2011;91(4):598–608.
22. Chouaib S, Messai Y, Couve S, Escudier B, Hasmim M, Noman MZ. Hypoxia promotes tumor growth in linking angiogenesis to immune escape. Front Immunol. 2012;3:21.
23. Li B, et al. Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy. Clin Cancer Res. 2006;12(22):6808–6816.
24. Terme M, et al. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 2013;73(2):539–549.
25. Adotevi O, et al. A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J Immunother. 2010;33(9):991–998.
26. Finke JH, et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res. 2008;14(20):6674–6682.
27. Wang Q, et al. Sorafenib reduces hepatic infiltrated regulatory T cells in hepatocellular carcinoma patients by suppressing TGF-beta signal. J Surg Oncol. 2013;107(4):422–427.
28. Monk P, et al. A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. J Immunother. 2014;37(3):180–186.
29. Cabrera R, et al. Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma. Cancer Immunol Immunother. 2013;62(4):737–746.
30. Franceschini D, et al. PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV. J Clin Invest. 2009;119(3):551–564.
31. Kalathil SG, et al. T-regulatory cells and programmed death 1+ T cells contribute to effector T-cell dysfunction in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;190(1):40–50.
32. Hommel G. A comparison of two modified Bonferroni procedures. Biometrika. 1989;76:624–625.