Immunity, cancer and aging: Lessons from mouse models

Aging and Disease

Volumn 2, Issue 6, 2011, Pages 512-523

  Myers, Cheryl E ^a   Mirza, Noweeda N ^a   Lustgarten, Joseph ^a  

^a MAYO CLINIC   (United States)

Author keywords

Aging; Cancer; Immunity; Immunotherapy; Intervention

Indexed keywords

EID: 84861201007     PISSN: None     EISSN: 21525250     Source Type: Journal    
DOI: None     Document Type: Review

References (105)

1. Miller RA (1991). Gerontology as oncology. Research on aging as the key to the understanding of cancer. Cancer, 68: 2496-2501
2. Yancik R (1997). Cancer burden in the aged: an epidemiologic and demographic overview. Cancer, 80: 1273-1283
3. Dunn GP, Bruce AT, Ikeda H, Old LJ and Schreiber RD (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol, 3: 991-998
4. Russell JH and Ley TJ (2002). Lymphocyte-mediated cytotoxicity. Annu. Rev. Immunol., 20: 323-370
5. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY and Godfrey DI (2000). Differential tumor surveillance by natural killer (NK) and NKT cells. J. Exp. Med., 191: 661-668
6. Street SE, Cretney E and Smyth MJ (2001). Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood, 97: 192-197
7. van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, Melief CJ, Zinkernagel RM and Hengartner H (1996). Decreased tumor surveillance in perforin-deficient mice. J. Exp. Med., 184: 1781-1790
8. Saurwein-Teissl M, Romani N and Grubeck-Loebenstein B (2000). Dendritic cells in old age--neglected by gerontology? Mech. Ageing Dev., 121: 123-130
9. Song L, Kim YH, Chopra RK, Proust JJ, Nagel JE, Nordin AA and Adler WH (1993). Age-related effects in T cell activation and proliferation. Exp. Gerontol., 28: 313-321
10. Taub DD and Longo DL (2005). Insights into thymic aging and regeneration. Immunol. Rev., 205: 72-93
11. Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M and Sansoni P (2000). Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood, 95: 2860-2868
12. Gupta S, Bi R, Su K, Yel L, Chiplunkar S and Gollapudi S (2004). Characterization of naive, memory and effector CD8+ T cells: effect of age. Exp. Gerontol., 39: 545-550
13. Thoman ML (1997). Effects of the aged microenvironment on CD4+ T cell maturation. Mech. Ageing Dev., 96: 75-88
14. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E and De Benedictis G (2000). Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci., 908: 244-254
15. Franceschi C (2007). Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr. Rev., 65: S173-176
16. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC and Salvioli S (2007). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev., 128: 92-105
17. Davalos AR, Coppe JP, Campisi J and Desprez PY (2010). Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev., 29: 273-283
18. Linton PJ, Li SP, Zhang Y, Bautista B, Huynh Q and Trinh T (2005). Intrinsic versus environmental influences on T-cell responses in aging. Immunol. Rev., 205: 207-219
19. Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, Franceschi C and Passeri M (2008). The immune system in extreme longevity. Exp. Gerontol., 43: 61-65
20. Loo DS (2007). Onychomycosis in the elderly: drug treatment options. Drugs Aging, 24: 293-302
21. McElhaney JE (2009). Prevention of infectious diseases in older adults through immunization: the challenge of the senescent immune response. Expert Rev Vaccines, 8: 593-606
22. Meyer KC (2004). Lung infections and aging. Ageing Res Rev, 3: 55-67
23. Mirza N, Pollock K, Hoelzinger DB, Dominguez AL and Lustgarten J (2011). Comparative kinetic analyses of gene profiles of naive CD4(+) and CD8(+) T cells from young and old animals reveal novel age-related alterations. Aging Cell, 10: 853-867
24. Janeway CA, Jr., Dianzani U, Portoles P, Rath S, Reich EP, Rojo J, Yagi J and Murphy DB (1989). Cross-linking and conformational change in T-cell receptors: role in activation and in repertoire selection. Cold Spring Harb. Symp. Quant. Biol., 54 Pt 2: 657-666
25. Trinchieri G and Sher A (2007). Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol, 7: 179-190
26. Kaisho T and Akira S (2003). Regulation of dendritic cell function through Toll-like receptors. Curr Mol Med, 3: 373-385
27. Takeda K, Kaisho T and Akira S (2003). Toll-like receptors. Annu. Rev. Immunol., 21: 335-376
28. Hawlisch H and Kohl J (2006). Complement and Toll-like receptors: key regulators of adaptive immune responses. Mol. Immunol., 43: 13-21
29. Kawarada Y, Ganss R, Garbi N, Sacher T, Arnold B and Hammerling GJ (2001). NK- and CD8(+) T cell-mediated eradication of established tumors by peritumoral injection of CpG-containing oligodeoxynucleotides. J. Immunol., 167: 5247-5253
30. Yang Y, Huang CT, Huang X and Pardoll DM (2004). Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat Immunol, 5: 508-515
31. Salem ML, Kadima AN, Cole DJ and Gillanders WE (2005). Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity. J. Immunother., 28: 220-228
32. Bullock TN and Yagita H (2005). Induction of CD70 on dendritic cells through CD40 or TLR stimulation contributes to the development of CD8+ T cell responses in the absence of CD4+ T cells. J. Immunol., 174: 710-717
33. Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J and Sambhara S (2002). Cutting edge: impaired Toll-like receptor expression and function in aging. J. Immunol., 169: 4697-4701
34. Boehmer ED, Goral J, Faunce DE and Kovacs EJ (2004). Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J. Leukoc. Biol., 75: 342-349
35. Sharma S, Dominguez AL, Hoelzinger DB and Lustgarten J (2008). CpG-ODN but not other TLR-ligands restore the antitumor responses in old mice: the implications for vaccinations in the aged. Cancer Immunol. Immunother., 57: 549-561
36. van Duin D and Shaw AC (2007). Toll-like receptors in older adults. J. Am. Geriatr. Soc., 55: 1438-1444
37. Miyara M and Sakaguchi S (2007). Natural regulatory T cells: mechanisms of suppression. Trends Mol Med, 13: 108-116
38. Sakaguchi S, Yamaguchi T, Nomura T and Ono M (2008). Regulatory T cells and immune tolerance. Cell, 133: 775-787
39. Hori S, Nomura T and Sakaguchi S (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science, 299: 1057-1061
40. Green EA, Gorelik L, McGregor CM, Tran EH and Flavell RA (2003). CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc. Natl. Acad. Sci. U. S. A., 100: 10878-10883
41. Samy ET, Parker LA, Sharp CP and Tung KS (2005). Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node. J. Exp. Med., 202: 771-781
42. Sharma S, Dominguez AL and Lustgarten J (2006). High accumulation of T regulatory cells prevents the activation of immune responses in aged animals. J. Immunol., 177: 8348-8355
43. Gregg R, Smith CM, Clark FJ, Dunnion D, Khan N, Chakraverty R, Nayak L and Moss PA (2005). The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age. Clin. Exp. Immunol., 140: 540-546
44. Lages CS, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, Belkaid Y and Chougnet C (2008). Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J. Immunol., 181: 1835-1848
45. Serafini P, Borrello I and Bronte V (2006). Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin. Cancer Biol., 16: 53-65
46. Nagaraj S and Gabrilovich DI (2008). Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res., 68: 2561-2563
47. Rodriguez PC and Ochoa AC (2008). Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol. Rev., 222: 180-191
48. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S and Carbone DP (1998). Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood, 92: 4150-4166
49. Young MR, Petruzzelli GJ, Kolesiak K, Achille N, Lathers DM and Gabrilovich DI (2001). Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34(+) progenitor cells. Hum. Immunol., 62: 332-341
50. Grizzle WE, Xu X, Zhang S, Stockard CR, Liu C, Yu S, Wang J, Mountz JD and Zhang HG (2007). Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice. Mech. Ageing Dev., 128: 672-680
51. Kusmartsev S, Nagaraj S and Gabrilovich DI (2005). Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J. Immunol., 175: 4583-4592
52. Bunt SK, Yang L, Sinha P, Clements VK, Leips J and Ostrand-Rosenberg S (2007). Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res., 67: 10019-10026
53. Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM and Chen SH (2006). Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res., 66: 1123-1131
54. Huang H, Patel DD and Manton KG (2005). The immune system in aging: roles of cytokines, T cells and NK cells. Front. Biosci., 10: 192-215
55. Fulop T, Larbi A, Douziech N, Levesque I, Varin A and Herbein G (2006). Cytokine receptor signalling and aging. Mech. Ageing Dev., 127: 526-537
56. Munn DH and Mellor AL (2007). Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest., 117: 1147-1154
57. Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C and Mellor AL (1998). Prevention of allogeneic fetal rejection by tryptophan catabolism. Science, 281: 1191-1193
58. Lin YC, Chen CL, Nakano T, Goto S, Kao YH, Hsu LW, Lai CY, Jawan B, Cheng YF, Tateno C and Yoshizato K (2008). Immunological role of indoleamine 2,3-dioxygenase in rat liver allograft rejection and tolerance. J. Gastroenterol. Hepatol., 23: e243-250
59. Brandacher G, Perathoner A, Ladurner R, Schneeberger S, Obrist P, Winkler C, Werner ER, Werner-Felmayer G, Weiss HG, Gobel G, Margreiter R, Konigsrainer A, Fuchs D and Amberger A (2006). Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin. Cancer Res., 12: 1144-1151
60. Ino K, Yoshida N, Kajiyama H, Shibata K, Yamamoto E, Kidokoro K, Takahashi N, Terauchi M, Nawa A, Nomura S, Nagasaka T, Takikawa O and Kikkawa F (2006). Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer. Br. J. Cancer, 95: 1555-1561
61. Friberg M, Jennings R, Alsarraj M, Dessureault S, Cantor A, Extermann M, Mellor AL, Munn DH and Antonia SJ (2002). Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int. J. Cancer, 101: 151-155
62. Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC and Munn DH (2007). Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res., 67: 792-801
63. Pertovaara M, Hasan T, Raitala A, Oja SS, Yli-Kerttula U, Korpela M and Hurme M (2007). Indoleamine 2,3-dioxygenase activity is increased in patients with systemic lupus erythematosus and predicts disease activation in the sunny season. Clin. Exp. Immunol., 150: 274-278
64. Greenwald RJ, Freeman GJ and Sharpe AH (2005). The B7 family revisited. Annu. Rev. Immunol., 23: 515-548
65. Zang X and Allison JP (2007). The B7 family and cancer therapy: costimulation and coinhibition. Clin. Cancer Res., 13: 5271-5279
66. Zou W and Chen L (2008). Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol, 8: 467-477
67. Korman AJ, Peggs KS and Allison JP (2006). Checkpoint blockade in cancer immunotherapy. Adv. Immunol., 90: 297-339
68. Wolchok JD and Saenger Y (2008). The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation. Oncologist, 13 Suppl 4: 2-9
69. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR and Honjo T (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med., 192: 1027-1034
70. Wang S, Bajorath J, Flies DB, Dong H, Honjo T and Chen L (2003). Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction. J. Exp. Med., 197: 1083-1091
71. Nishimura H, Nose M, Hiai H, Minato N and Honjo T (1999). Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 11: 141-151
72. Dong H, Zhu G, Tamada K, Flies DB, van Deursen JM and Chen L (2004). B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity, 20: 327-336
73. Strome SE, Dong H, Tamura H, Voss SG, Flies DB, Tamada K, Salomao D, Cheville J, Hirano F, Lin W, Kasperbauer JL, Ballman KV and Chen L (2003). B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res., 63: 6501-6505
74. Blank C, Gajewski TF and Mackensen A (2005). Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol. Immunother., 54: 307-314
75. Dong H, Strome SE, Matteson EL, Moder KG, Flies DB, Zhu G, Tamura H, Driscoll CL and Chen L (2003). Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. J. Clin. Invest., 111: 363-370
76. Wang S, Zhu G, Chapoval AI, Dong H, Tamada K, Ni J and Chen L (2000). Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS. Blood, 96: 2808-2813
77. Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, Dong H, Sica GL, Zhu G, Tamada K and Chen L (2001). B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol, 2: 269-274
78. Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J and Chen L (2003). B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity, 18: 849-861
79. Hurwitz AA, Kwon ED and van Elsas A (2000). Costimulatory wars: the tumor menace. Curr. Opin. Immunol., 12: 589-596
80. Prilliman KR, Lemmens EE, Palioungas G, Wolfe TG, Allison JP, Sharpe AH and Schoenberger SP (2002). Cutting edge: a crucial role for B7-CD28 in transmitting T help from APC to CTL. J. Immunol., 169: 4094-4097
81. Li Y, McGowan P, Hellstrom I, Hellstrom KE and Chen L (1994). Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J. Immunol., 153: 421-428
82. Raes G, Van Ginderachter J, Liu YQ, Brys L, Thielemans K, De Baetselier P and Geldhof A (1998). Active antitumor immunotherapy, with or without B7-mediated costimulation, increases tumor progression in an immunogenic murine T cell lymphoma model. Cancer Immunol. Immunother., 45: 257-265
83. Morel Y, Truneh A, Sweet RW, Olive D and Costello RT (2001). The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity. J. Immunol., 167: 2479-2486
84. Gramaglia I, Weinberg AD, Lemon M and Croft M (1998). Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J. Immunol., 161: 6510-6517
85. Rogers PR, Song J, Gramaglia I, Killeen N and Croft M (2001). OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity, 15: 445-455
86. Weatherill AR, Maxwell JR, Takahashi C, Weinberg AD and Vella AT (2001). OX40 ligation enhances cell cycle turnover of Ag-activated CD4 T cells in vivo. Cell. Immunol., 209: 63-75
87. Weinberg AD, Rivera MM, Prell R, Morris A, Ramstad T, Vetto JT, Urba WJ, Alvord G, Bunce C and Shields J (2000). Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J. Immunol., 164: 2160-2169
88. Lustgarten J, Dominguez AL and Thoman M (2004). Aged mice develop protective antitumor immune responses with appropriate costimulation. J. Immunol., 173: 4510-4515
89. Sharma S, Dominguez AL and Lustgarten J (2006). Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB. Exp. Gerontol., 41: 78-84
90. Bansal-Pakala P and Croft M (2002). Defective T cell priming associated with aging can be rescued by signaling through 4-1BB (CD137). J. Immunol., 169: 5005-5009
91. Ruby CE and Weinberg AD (2009). The effect of aging on OX40 agonist-mediated cancer immunotherapy. Cancer Immunol. Immunother., 58: 1941-1947
92. Ruby CE and Weinberg AD (2009). OX40-enhanced tumor rejection and effector T cell differentiation decreases with age. J. Immunol., 182: 1481-1489
93. Grolleau-Julius A, Garg MR, Mo R, Stoolman LL and Yung RL (2006). Effect of aging on bone marrow-derived murine CD11c+CD4-CD8alpha- dendritic cell function. J. Gerontol. A. Biol. Sci. Med. Sci., 61: 1039-1047
94. Provinciali M, Argentati K and Tibaldi A (2000). Efficacy of cancer gene therapy in aging: adenocarcinoma cells engineered to release IL-2 are rejected but do not induce tumor specific immune memory in old mice. Gene Ther., 7: 624-632
95. Provinciali M, Smorlesi A, Donnini A, Bartozzi B and Amici A (2003). Low effectiveness of DNA vaccination against HER-2/neu in ageing. Vaccine, 21: 843-848
96. Gravekamp C, Sypniewska R, Gauntt S, Tarango M, Price P and Reddick R (2004). Behavior of metastatic and nonmetastatic breast tumors in old mice. Exp Biol Med (Maywood), 229: 665-675
97. Marigo I, Dolcetti L, Serafini P, Zanovello P and Bronte V (2008). Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol. Rev., 222: 162-179
98. Muller WJ, Sinn E, Pattengale PK, Wallace R and Leder P (1988). Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell, 54: 105-115
99. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD and Muller WJ (1992). Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc. Natl. Acad. Sci. U. S. A., 89: 10578-10582
100. Lustgarten J, Dominguez AL and Cuadros C (2004). The CD8+ T cell repertoire against Her-2/neu antigens in neu transgenic mice is of low avidity with antitumor activity. Eur. J. Immunol., 34: 752-761
101. Lustgarten J, Dominguez AL and Pinilla C (2006). Identification of cross-reactive peptides using combinatorial libraries circumvents tolerance against Her-2/neu-immunodominant epitope. J. Immunol., 176: 1796-1805
102. Lustgarten J, Theobald M, Labadie C, LaFace D, Peterson P, Disis ML, Cheever MA and Sherman LA (1997). Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD.8. Hum. Immunol., 52: 109-118
103. Cuadros C, Dominguez AL, Frost GI, Borgstrom P and Lustgarten J (2003). Cooperative effect between immunotherapy and antiangiogenic therapy leads to effective tumor rejection in tolerant Her-2/neu mice. Cancer Res., 63: 5895-5901
104. Cuadros C, Dominguez AL, Lollini PL, Croft M, Mittler RS, Borgstrom P and Lustgarten J (2005). Vaccination with dendritic cells pulsed with apoptotic tumors in combination with anti-OX40 and anti-4-1BB monoclonal antibodies induces T cell mediated protective immunity in Her-2/neu transgenic mice. Int. J. Cancer, 116: 934-943
105. Dominguez AL and Lustgarten J (2008). Implications of aging and self-tolerance on the generation of immune and antitumor immune responses. Cancer Res., 68: 5423-5431