Rapamycin impairs antitumor CD8p T-cell responses and vaccine-induced tumor eradication

Cancer Research

Volumn 75, Issue 16, 2015, Pages 3279-3291

  Chaoul, Nada ^a,b   Fayolle, Catherine ^a,b   Desrues, Belinda ^a,b   Oberkampf, Marine ^a,b   Tang, Alexandre ^a,b   Ladant, Daniel ^a,c   Leclerc, Claude ^a,b  

^a INSTITUT PASTEUR   (France)

^b INSERM   (France)

^c CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADJUVANT; HUMAN PAPILLOMAVIRUS TYPE E7 VACCINE; RAPAMYCIN; UNCLASSIFIED DRUG; WART VIRUS VACCINE; ANTINEOPLASTIC ANTIBIOTIC; CANCER VACCINE; MTOR PROTEIN, MOUSE; PROTEIN E7; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER IMMUNIZATION; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENTIATION; FEMALE; HUMAN PAPILLOMAVIRUS TYPE E7; IMMUNE RESPONSE; IN VIVO STUDY; LOW DRUG DOSE; LYMPHOCYTIC INFILTRATION; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SUPPRESSOR CELL; TUMOR REGRESSION; UTERINE CERVIX CANCER; WART VIRUS; ANIMAL; ANTAGONISTS AND INHIBITORS; BONE MARROW CELL; C57BL MOUSE; DISEASE MODEL; DRUG EFFECTS; FLOW CYTOMETRY; HUMAN; IMMUNOLOGY; METABOLISM; NEOPLASMS; TUMOR CELL LINE; TUMOR VOLUME;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; CANCER VACCINES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; FEMALE; FLOW CYTOMETRY; HUMANS; MICE, INBRED C57BL; MYELOID CELLS; NEOPLASMS; PAPILLOMAVIRUS E7 PROTEINS; SIROLIMUS; T-LYMPHOCYTES, CYTOTOXIC; T-LYMPHOCYTES, REGULATORY; TOR SERINE-THREONINE KINASES; TUMOR BURDEN;

EID: 84942847541     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-15-0454     Document Type: Article

References (50)

1. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012;149:274-93.
2. Nguyen SA,Walker D, Gillespie MB, Gutkind JS, Day TA. mTOR inhibitors and its role in the treatment of head and neck squamous cell carcinoma. Curr Treat Options Oncol 2012;13:71-81.
3. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006;124:471-84.
4. Amornphimoltham P, Patel V, Sodhi A, Nikitakis NG, Sauk JJ, Sausville EA, Molinolo AA, Gutkind JS. Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck. Cancer Res 2005;65:9953-61.
5. Faivre S, Kroemer G,Raymond E. Current development ofmTORinhibitors as anticancer agents. Nat Rev Drug Discov 2006;5:671-88.
6. Ji J, Zheng PS. Activation of mTOR signaling pathway contributes to survival of cervical cancer cells. Gynecol Oncol 2010; 117:103-8.
7. Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB, et al. Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res 2004;10:7031-42.
8. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.N Engl J Med 2007;356:2271-81.
9. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
10. Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009;27:2278-87.
11. Powell JD, Pollizzi KN, Heikamp EB, Horton MR. Regulation of immune responses by mTOR. Annu Rev Immunol 2012;30:39-68.
12. Chi H. Regulation and function ofmTOR signalling in T cell fate decisions. Nat Rev Immunol 2012;12:325-38.
13. Powell JD, Delgoffe GM. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 2010;33: 301-11.
14. Araki K, Turner AP, Shaffer VO,Gangappa S, Keller SA, BachmannMF, et al. mTOR regulates memory CD8 T-cell differentiation. Nature 2009;460: 108-12.
15. Li Q, Rao R, Vazzana J, Goedegebuure P, Odunsi K, Gillanders W, et al. Regulating mammalian target of rapamycin to tune vaccinationinduced CD8(p) T cell responses for tumor immunity. J Immunol 2012;188:3080-7.
16. Turner AP, Shaffer VO, Araki K, Martens C, Turner PL, Gangappa S, et al. Sirolimus enhances the magnitude and quality of viral-specific CD8p T-cell responses to vaccinia virus vaccination in rhesus macaques. Am J Transplant 2011;11:613-8.
17. Munger K. The role of human papillomaviruses in human cancers. Front Biosci 2002;7:d641-9.
18. Preville X, Ladant D, Timmerman B, Leclerc C. Eradication of established tumors by vaccination with recombinant Bordetella pertussis adenylate cyclase carrying the human papillomavirus 16 E7 oncoprotein. Cancer Res 2005;65:641-9.
19. Berraondo P, Nouze C, Preville X, Ladant D, Leclerc C. Eradication of large tumors in mice by a tritherapy targeting the innate, adaptive, and regulatory components of the immune system. Cancer Res 2007;67:8847-55.
20. Lin KY, Guarnieri FG, Staveley-O'Carroll KF, Levitsky HI, August JT, Pardoll DM, et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 1996;56:21-6.
21. Feltkamp MC, Smits HL, Vierboom MP, Minnaar RP, de Jongh BM, Drijfhout JW, et al. Vaccination with cytotoxic T lymphocyte epitopecontaining peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol 1993;23:2242-9.
22. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.
23. Schouppe E, Van Overmeire E, Laoui D, Keirsse J, Van Ginderachter JA. Modulation of CD8(p) T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells. Immunobiology 2013;218: 1385-91.
24. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008;26:677-704.
25. Sainz-Perez A, Lim A, Lemercier B, Leclerc C. The T-cell receptor repertoire of tumor-infiltrating regulatory T lymphocytes is skewed towards public sequences. Cancer Res 2012;72:3557-69.
26. Nocentini G, Riccardi C. GITR: a modulator of immune response and inflammation. Adv Exp Med Biol 2009;647:156-73.
27. Wang Y, Wang XY, Subjeck JR, Shrikant PA, Kim HL. Temsirolimus, an mTORinhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. Br J Cancer 2011;104:643-52.
28. Moschella F, Torelli GF, Valentini M, Urbani F, Buccione C, Petrucci MT, et al. Cyclophosphamide induces a type I interferon-associated sterile inflammatory response signature in cancer patients' blood cells: implications for cancer chemoimmunotherapy. Clin Cancer Res 2013;19: 4249-61.
29. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, et al. Metronomic cyclophosphamide regimen selectively depletes CD4pCD25p regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007;56: 641-8.
30. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 2013;38:729-41.
31. Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1p/CD11bp myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 2005;11:6713-21.
32. Vincent J,Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 2010;70:3052-61.
33. Bruchard M, Mignot G, Derangere V, Chalmin F, Chevriaux A, Vegran F, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med 2013;19:57-64.
34. Hess G. Temsirolimus for the treatment of mantle cell lymphoma. Expert Rev Hematol 2009;2:631-40.
35. Easton JB, Houghton PJ. mTOR and cancer therapy. Oncogene 2006;25: 6436-46.
36. Salgo R, Gossmann J, Schofer H, Kachel HG, Kuck J, Geiger H, et al. Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant 2010;10:1385-93.
37. Schena FP, Pascoe MD, Alberu J, del Carmen RialM, Oberbauer R, Brennan DC, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009;87:233-42.
38. Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009;30:832-44.
39. Coenen JJ, Koenen HJ, van Rijssen E, Kasran A, Boon L, Hilbrands LB, et al. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4p CD25p FoxP3p T cells. Bone Marrow Transplant 2007;39:537-45.
40. Berezhnoy A, Castro I, Levay A, Malek TR, Gilboa E. Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity. J Clin Invest 2014;124:188-97.
41. Ferrer IR, Wagener ME, Robertson JM, Turner AP, Araki K, Ahmed R, et al. Cutting edge: Rapamycin augments pathogen-specific but not graft-reactive CD8p T cell responses. J Immunol 2010;185:2004-8.
42. Motzer RJ, HudesGR, Curti BD,McDermott DF, Escudier BJ, Negrier S, et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol 2007;25:3958-64.
43. MacDonald A, Scarola J, Burke JT, Zimmerman JJ. Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus. Clin Therapeut 2000;22 Suppl B:B101-21.
44. Lebwohl D, Anak O, Sahmoud T, Klimovsky J, Elmroth I, Haas T, et al. Development of everolimus, a novel oral mTOR inhibitor, across a spectrum of diseases. Ann N Y Acad Sci 2013;1291:14-32.
45. Hiraoka K, Miyamoto M, Cho Y, Suzuoki M, Oshikiri T, Nakakubo Y, et al. Concurrent infiltration by CD8p T cells and CD4p T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 2006; 94:275-80.
46. Menegaz RA, Michelin MA, Etchebehere RM, Fernandes PC,Murta EF. Periand intratumoral T and B lymphocytic infiltration in breast cancer. Eur J Gynaecol Oncol 2008;29:321-6.
47. Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, et al. In situ cytotoxic andmemory T cells predict outcome in patients with earlystage colorectal cancer. J Clin Oncol 2009;27:5944-51.
48. Galon J, Angell HK, Bedognetti D, Marincola FM. The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity 2013;39:11-26.
49. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942-9.
50. Merlo A, Casalini P, Carcangiu ML,Malventano C, Triulzi T,Menard S, et al. FOXP3 expression and overall survival in breast cancer. J Clin Oncol 2009;27:1746-52.