The convergence of radiation and immunogenic cell death signaling pathways

Encouse B Golden, Ilenia Pellicciotta, Sandra Demaria, Mary H Barcellos-Hoff, Silvia C Formenti, Encouse B Golden, Ilenia Pellicciotta, Sandra Demaria, Mary H Barcellos-Hoff, Silvia C Formenti

Abstract

Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival.

Keywords: apoptosis; autophagy; immunogenic cell death; ionizing radiation; mitotic catastrophe; necrosis; senescence.

Figures

Figure 1
Figure 1
Apoptosis and necrosis. IR-induced apoptosis through the intrinsic apoptotic pathway begins with the development of DNA DSBs. ATM and CHK2 associated p53 phosphorylation events result in the nuclear accumulation of transcriptionally active p53, which in turn transactivates the pro-apoptotic genes PUMA, Bax, and Noxa. Cytoplasmic PUMA disrupts the Bcl-XL/p53 complex and liberates p53. Free cytoplasmic p53 disrupts the Bcl2/Bax complex by associating with the anti-apoptotic protein Bcl2 and releasing the pro-apoptotic protein Bax. Bax triggers cell death through the release of cytochrome c from the mitochondria, resulting in apoptosome formation and activation effector caspases and apoptosis. The extrinsic pathway involves signaling through death receptors. IR activation of p53, results in downstream transactivation of CD95/Fas and the CD95/Fas ligand. CD95/Fas ligand binding to CD95/Fas induces trimerization and clustering of the intracellular death domain (DD) region of the receptor. The DD recruits the adaptor protein, Fas-associated death domain (FADD). The death effector domain of FADD recruits pro-caspase-8, forming the death-inducing signaling complex. Activation of the initiator caspase-8 leads to activation of effector caspases and apoptosis. Additionally, IR-induced membrane stress leads to ceramide production, second messenger signaling, and apoptosis. RIP1 protein is associated with the FADD and is a key upstream kinase involved in the activation of regulated necrosis. Regulated necrosis is sustained in death receptor stimulated cells that are caspase-8 deficient or inhibited.
Figure 2
Figure 2
Mitotic catastrophe and senescence. Mitotic catastrophe (MC) occurs after failed mitosis. Cells are characterized by an increased frequency of multiple nuclei and micronuclei. Checkpoint control is greatly reduced in mutant p53 tumor cells, making the cells susceptible to premature mitosis, chromosomal dysegregation, the generation of aneuploid progeny, and MC associated cell death. Senescence on the other hand, is a form of irreversible growth arrest that halts the proliferation of metabolically active cells. IR-induced accelerated senescence in tumor cells is centered around p53. When IR induced DSBs result in p53 activation, activated p53 promotes the activity of p21, an inhibitor of CDK/cyclin complexes and cell cycle progression. Senescent cells display the loss of replicative potential, cell cycle arrest, and enlarged and flattened morphology.
Figure 3
Figure 3
Autophagy. The MAPK/erk 1/2 and PI3K-I/AKT signaling pathways block the promotion of autophagy via the activation of MTOR. IR-induced DNA damage activates p53, which acts as a negative regulator of MTOR. Upon initiation of autophagy, the phagophore is generated. A class III PI3K complex (Beclin, class III PI3K, and p150) recruits LC3 to the membrane and facilitates membrane expansion. Complete sequestration by the elongating phagophore results in autophagosome formation. After formation, the autophagosome fuses with the lysosome to become an autophagolysosome, where lysosomal hydrolases digest the sequestered cytoplasmic derived contents.
Figure 4
Figure 4
Immunogenic cell death. Three distinct arms orchestrate ICD in dying tumor cells and are required for immune priming and activation: (1) the cell surface translocation of calreticulin (CRT) and the extracellular release of (2) HMGB1 and (3) ATP. CRT cell surface exposure acts as a dendritic cell “eat me signal” and involves the coordinated activation of 3 specific modules: ER stress, apoptosis, and ER-Golgi trafficking and extracellular exposure of CRT. HMGB1 is passively released from dying tumor cells and acts as a cytokine and danger associated molecular pattern protein that mediates responses to infection, injury, and inflammation. ATP is released from dying tumor cells and involves the autophagic machinery. Extracellular ATP activates the dendritic cell (DC) P2X7 receptor, which is involved in the upregulation and activation of the DC inflammasome.

References

    1. Apetoh L., Ghiringhelli F., Tesniere A., Obeid M., Ortiz C., Criollo A., Mignot G., Maiuri M. C., Ullrich E., Saulnier P., Yang H., Amigorena S., Ryffel B., Barrat F. J., Saftig P., Levi F., Lidereau R., Nogues C., Mira J. P., Chompret A., Joulin V., Clavel-Chapelon F., Bourhis J., Andre F., Delaloge S., Tursz T., Kroemer G., Zitvogel L. (2007). Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13, 1050–1059 10.1586/1744666X.4.1.27
    1. Barcellos-Hoff M. H., Park C., Wright E. G. (2005). Radiation and the microenvironment—tumorigenesis and therapy. Nat. Rev. Cancer 5, 867–875 10.1038/nrc1735
    1. Bernales S., Schuck S., Walter P. (2007). ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy 3, 285–287
    1. Bursch W., Karwan A., Mayer M., Dornetshuber J., Frohwein U., Schulte-Hermann R., Fazi B., Di Sano F., Piredda L., Piacentini M., Petrovski G., Fesus L., Gerner C. (2008). Cell death and autophagy: cytokines, drugs, and nutritional factors. Toxicology 254, 147–157 10.1016/j.tox.2008.07.048
    1. Cain K., Brown D. G., Langlais C., Cohen G. M. (1999). Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex. J. Biol. Chem. 274, 22686–22692
    1. Castedo M., Perfettini J. L., Roumier T., Yakushijin K., Horne D., Medema R., Kroemer G. (2004). The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe. Oncogene 23, 4353–4361 10.1038/sj.onc.1207573
    1. Chaachouay H., Ohneseit P., Toulany M., Kehlbach R., Multhoff G., Rodemann H. P. (2011). Autophagy contributes to resistance of tumor cells to ionizing radiation. Radiother. Oncol. 99, 287–292 10.1016/j.radonc.2011.06.002
    1. Chakravarty P. K., Alfieri A., Thomas E. K., Beri V., Tanaka K. E., Vikram B., Guha C. (1999). Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer. Cancer Res. 59, 6028–6032
    1. Chen N., Karantza-Wadsworth V. (2009). Role and regulation of autophagy in cancer. Biochim. Biophys. Acta. 9, 1516–1523 10.1016/j.bbamcr.2008.12.013
    1. Chen Y. S., Song H. X., Lu Y., Li X., Chen T., Zhang Y., Xue J. X., Liu H., Kan B., Yang G., Fu T. (2011). Autophagy inhibition contributes to radiation sensitization of esophageal squamous carcinoma cells. Dis. Esophagus 24, 437–443 10.1111/j.1442-2050.2010.01156.x
    1. Chipuk J. E., Bouchier-Hayes L., Kuwana T., Newmeyer D. D., Green D. R. (2005). PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309, 1732–1735 10.1126/science.1114297
    1. Chrcanovic B. R., Reher P., Sousa A. A., Harris M. (2010). Osteoradionecrosis of the jaws–a current overview–part 1, Physiopathology and risk and predisposing factors. Oral Maxillofac. Surg. 14, 3–16 10.1007/s10006-009-0198-9
    1. Clarke M., Collins R., Darby S., Davies C., Elphinstone P., Evans E., Godwin J., Gray R., Hicks C., James S., Mackinnon E., McGale P., McHugh T., Peto R., Taylor C., Wang Y. (2005). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366, 2087–2106 10.1016/S0140-6736(05)67887-7
    1. Coppe J. P., Desprez P. Y., Krtolica A., Campisi J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 10.1146/annurev-pathol-121808-102144
    1. Cortez D., Wang Y., Qin J., Elledge S. J. (1999). Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286, 1162–1166 10.1126/science.286.5442.1162
    1. Crompton N. E. (1997). Telomeres, senescence and cellular radiation response. Cell. Mol. Life Sci. 53, 568–575
    1. Cuddihy A. R., Bristow R. G. (2004). The p53 protein family and radiation sensitivity: yes or no? Cancer Metastasis Rev. 23, 237–257 10.1023/B:CANC.0000031764.81141.e4
    1. Darby S., McGale P., Correa C., Taylor C., Arriagada R., Clarke M., Cutter D., Davies C., Ewertz M., Godwin J., Gray R., Pierce L., Whelan T., Wang Y., Peto R. (2011). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10, 801 women in 17 randomised trials. Lancet 378, 1707–1716 10.1016/S0140-6736(11)61629-2
    1. Declercq W., Vanden Berghe T., Vandenabeele P. (2009). RIP kinases at the crossroads of cell death and survival. Cell 138, 229–232 10.1016/j.cell.2009.07.006
    1. Degterev A., Hitomi J., Germscheid M., Ch'en I. L., Korkina O., Teng X., Abbott D., Cuny G. D., Yuan C., Wagner G., Hedrick S. M., Gerber S. A., Lugovskoy A., Yuan J. (2008). Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4, 313–321 10.1038/nchembio.83
    1. Dejean L. M., Martinez-Caballero S., Manon S., Kinnally K. W. (2006). Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins. Biochim. Biophys. Acta 1762, 191–201 10.1016/j.bbadis.2005.07.002
    1. Demaria S., Kawashima N., Yang A. M., Devitt M. L., Babb J. S., Allison J. P., Formenti S. C. (2005). Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin. Cancer Res. 11, 728–734
    1. Demaria S., Ng B., Devitt M. L., Babb J. S., Kawashima N., Liebes L., Formenti S. C. (2004). Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int. J. Radiat. Oncol. Biol. Phys. 58, 862–870 10.1016/j.ijrobp.2003.09.012
    1. Dewan M. Z., Galloway A. E., Kawashima N., Dewyngaert J. K., Babb J. S., Formenti S. C., Demaria S. (2009). Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin. Cancer Res. 15, 5379–5388 10.1158/1078-0432.CCR-09-0265
    1. Dogu Y., Diaz J. (2009). Mathematical model of a network of interaction between p53 and Bcl-2 during genotoxic-induced apoptosis. Biophys. Chem. 143, 44–54 10.1016/j.bpc.2009.03.012
    1. Dornan D., Shimizu H., Perkins N. D., Hupp T. R. (2003). DNA-dependent acetylation of p53 by the transcription coactivator p300. J. Biol. Chem. 278, 13431–13441 10.1074/jbc.M211460200
    1. Dumaz N., Meek D. W. (1999). Serine15 phosphorylation stimulates p53 transactivation but does not directly influence interaction with HDM2. EMBO J. 18, 7002–7010 10.1093/emboj/18.24.7002
    1. Ehlers G., Fridman M. (1973). Abscopal effect of radiation in papillary adenocarcinoma. Br. J. Radiol. 46, 220–222
    1. Eriksson D., Stigbrand T. (2010). Radiation-induced cell death mechanisms. Tumour Biol. 31, 363–372 10.1007/s13277-010-0042-8
    1. Fagagna F. D. A. D., Reaper P. M., Clay-Farrace L., Fiegler H., Carr P., Von Zglinicki T., Saretzki G., Carter N. P., Jackson S. P. (2003). A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 10.1038/nature02118
    1. Feng Z., Zhang H., Levine A. J., Jin S. (2005). The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. U.S.A. 102, 8204–8209 10.1073/pnas.0502857102
    1. Fink J., Born D., Chamberlain M. C. (2012). Radiation necrosis: relevance with respect to treatment of primary and secondary brain tumors. Curr. Neurol. Neurosci. Rep. 12, 276–285 10.1007/s11910-012-0258-7
    1. Formenti S. C., Demaria S. (2008). Effects of chemoradiation on tumor-host interactions: the immunologic side. J. Clin. Oncol. 26, 1562–1563 10.1200/JCO.2007.15.5499
    1. Formenti S. C., Demaria S. (2009). Systemic effects of local radiotherapy. Lancet Oncol. 10, 718–726 10.1016/S1470-2045(09)70082-8
    1. Fuchs Y., Steller H. (2011). Programmed cell death in animal development and disease. Cell 147, 742–758 10.1016/j.cell.2011.10.033
    1. Fujiwara K., Iwado E., Mills G. B., Sawaya R., Kondo S., Kondo Y. (2007). Akt inhibitor shows anticancer and radiosensitizing effects in malignant glioma cells by inducing autophagy. Int. J. Oncol. 31, 753–760
    1. Galluzzi L., Kroemer G. (2008). Necroptosis: a specialized pathway of programmed necrosis. Cell 135, 1161–1163 10.1016/j.cell.2008.12.004
    1. Garcia-Barros M., Paris F., Cordon-Cardo C., Lyden D., Rafii S., Haimovitz-Friedman A., Fuks Z., Kolesnick R. (2003). Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 300, 1155–1159 10.1126/science.1082504
    1. Garg A. D., Nowis D., Golab J., Vandenabeele P., Krysko D. V., Agostinis P. (2010). Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim. Biophys. Acta 1805, 53–71 10.1016/j.bbcan.2009.08.003
    1. Gewirtz D. A. (2007). Autophagy as a mechanism of radiation sensitization in breast tumor cells. Autophagy 3, 249–250
    1. Gewirtz D. A., Hilliker M. L., Wilson E. N. (2009). Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells. Radiother. Oncol. 92, 323–328 10.1016/j.radonc.2009.05.022
    1. Giusti A. M., Raimondi M., Ravagnan G., Sapora O., Parasassi T. (1998). Human cell membrane oxidative damage induced by single and fractionated doses of ionizing radiation: a fluorescence spectroscopy study. Int. J. Radiat. Biol. 74, 595–605
    1. Glynne-Jones R., Hoskin P. (2007). Neoadjuvant cisplatin chemotherapy before chemoradiation: a flawed paradigm? J. Clin. Oncol. 25, 5281–5286 10.1200/JCO.2007.12.3133
    1. Green D. R., Ferguson T., Zitvogel L., Kroemer G. (2009). Immunogenic and tolerogenic cell death. Nat. Rev. Immunol. 9, 353–363 10.1038/nri2545
    1. Gudkov A. V., Komarova E. A. (2003). The role of p53 in determining sensitivity to radiotherapy. Nat. Rev. Cancer 3, 117–129 10.1038/nrc992
    1. Harms K., Nozell S., Chen X. (2004). The common and distinct target genes of the p53 family transcription factors. Cell. Mol. Life Sci. 61, 822–842 10.1007/s00018-003-3304-4
    1. Hirose Y., Katayama M., Mirzoeva O. K., Berger M. S., Pieper R. O. (2005). Akt activation suppresses Chk2-mediated, methylating agent-induced G2 arrest and protects from temozolomide-induced mitotic catastrophe and cellular senescence. Cancer Res. 65, 4861–4869 10.1158/0008-5472.CAN-04-2633
    1. Holler N., Zaru R., Micheau O., Thome M., Attinger A., Valitutti S., Bodmer J. L., Schneider P., Seed B., Tschopp J. (2000). Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat. Immunol. 1, 489–495 10.1038/82732
    1. Hotchkiss R. S., Strasser A., McDunn J. E., Swanson P. E. (2009). Cell death. N. Engl. J. Med. 361, 1570–1583 10.1056/NEJMra0901217
    1. Huang J., Klionsky D. J. (2007). Autophagy and human disease. Cell Cycle 6, 1837–1849 10.4161/cc.6.15.4511
    1. Huang Q., Shen H. M. (2009). To die or to live: the dual role of poly(ADP-ribose) polymerase-1 in autophagy and necrosis under oxidative stress and DNA damage. Autophagy 5, 273–276 10.4161/auto.5.2.7640
    1. Ianzini F., Bertoldo A., Kosmacek E. A., Phillips S. L., Mackey M. A. (2006). Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells. Cancer Cell Int. 6, 11 10.1186/1475-2867-6-11
    1. Ito H., Daido S., Kanzawa T., Kondo S., Kondo Y. (2005). Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int. J. Oncol. 26, 1401–1410
    1. Jonathan E. C., Bernhard E. J., McKenna W. G. (1999). How does radiation kill cells? Curr. Opin. Chem. Biol. 3, 77–83 10.1016/S1367-5931(99)80014-3
    1. Jones K. R., Elmore L. W., Jackson-Cook C., Demasters G., Povirk L. F., Holt S. E., Gewirtz D. A. (2005). p53-Dependent accelerated senescence induced by ionizing radiation in breast tumour cells. Int. J. Radiat. Biol. 81, 445–458
    1. Kepp O., Galluzzi L., Martins I., Schlemmer F., Adjemian S., Michaud M., Sukkurwala A. Q., Menger L., Zitvogel L., Kroemer G. (2011). Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev. 30, 61–69 10.1007/s10555-011-9273-4
    1. Khandelwal S., van Rooijen N., Saxena R. K. (2007). Reduced expression of CD47 during murine red blood cell (RBC) senescence and its role in RBC clearance from the circulation. Transfusion 47, 1725–1732 10.1111/j.1537-2995.2007.01348.x
    1. Kim H., Bernard M. E., Flickinger J., Epperly M. W., Wang H., Dixon T. M., Shields D., Houghton F., Zhang X., Greenberger J. S. (2011). The autophagy-inducing drug carbamazepine is a radiation protector and mitigator. Int. J. Radiat. Biol. 87, 1052–1060 10.3109/09553002.2011.587860
    1. Kim S. T., Xu B., Kastan M. B. (2002). Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev. 16, 560–570 10.1101/gad.970602
    1. Kroemer G., Adjemian S., Michaud M., Martins I., Kepp O., Sukkurwala A. Q., Menger L., Vacchelli E., Ma Y., Zitvogel L. (2011). Contributions of immunogenic cell death to the efficacy of anticancer chemotherapy. Bull. Mem. Acad. R. Med. Belg. 166, 130–138 discussion: 139–140.
    1. Krumschnabel G., Sohm B., Bock F., Manzl C., Villunger A. (2009). The enigma of caspase-2, the laymen's view. Cell Death Differ. 16, 195–207 10.1038/cdd.2008.170
    1. Kuribayashi K., Finnberg N., Jeffers J. R., Zambetti G. P., El-Deiry W. S. (2011). The relative contribution of pro-apoptotic p53-target genes in the triggering of apoptosis following DNA damage in vitro and in vivo. Cell Cycle 10, 2380–2389 10.4161/cc.10.14.16588
    1. Kuwahara Y., Oikawa T., Ochiai Y., Roudkenar M. H., Fukumoto M., Shimura T., Ohtake Y., Ohkubo Y., Mori S., Uchiyama Y., Fukumoto M. (2011). Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy. Cell Death Dis. 2, e177 10.1038/cddis.2011.56
    1. Lane D. P. (1992). Cancer. p53, guardian of the genome. Nature 358, 15–16 10.1038/358015a0
    1. Lehmann B. D., McCubrey J. A., Jefferson H. S., Paine M. S., Chappell W. H., Terrian D. M. (2007). A dominant role for p53-dependent cellular senescence in radiosensitization of human prostate cancer cells. Cell Cycle 6, 595–605 10.4161/cc.6.5.3901
    1. Li J., Ni M., Lee B., Barron E., Hinton D. R., Lee A. S. (2008). The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells. Cell Death Differ. 15, 1460–1471 10.1038/cdd.2008.81
    1. Li Y., Zhang J., Chen X., Liu T., He W., Chen Y., Zeng X. (2012). Molecular machinery of autophagy and its implication in cancer. Am. J. Med. Sci. 343, 155–161 10.1097/MAJ.0b013e31821f978d
    1. Lin Y., Devin A., Rodriguez Y., Liu Z. G. (1999). Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 13, 2514–2526
    1. Lotze M. T., Tracey K. J. (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331–342 10.1038/nri1594
    1. Luce A., Courtin A., Levalois C., Altmeyer-Morel S., Romeo P. H., Chevillard S., Lebeau J. (2009). Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells. Carcinogenesis 30, 432–439 10.1093/carcin/bgp008
    1. Lukas J., Lukas C., Bartek J. (2004). Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair (Amst.) 3, 997–1007 10.1016/j.dnarep.2004.03.006
    1. Ma Y., Kepp O., Ghiringhelli F., Apetoh L., Aymeric L., Locher C., Tesniere A., Martins I., Ly A., Haynes N. M., Smyth M. J., Kroemer G., Zitvogel L. (2010). Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin. Immunol. 22, 113–124 10.1016/j.smim.2010.03.001
    1. Maltzman W., Czyzyk L. (1984). UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol. Cell. Biol. 4, 1689–1694 10.1128/MCB.4.9.1689
    1. Marzo I., Brenner C., Zamzami N., Jurgensmeier J. M., Susin S. A., Vieira H. L., Prevost M. C., Xie Z., Matsuyama S., Reed J. C., Kroemer G. (1998). Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281, 2027–2031 10.1126/science.281.5385.2027
    1. Maxhimer J. B., Soto-Pantoja D. R., Ridnour L. A., Shih H. B., Degraff W. G., Tsokos M., Wink D. A., Isenberg J. S., Roberts D. D. (2009). Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci. Transl. Med. 1, 3ra7 10.1126/scitranslmed.3000139
    1. Mendonca M. S., Chin-Sinex H., Dhaemers R., Mead L. E., Yoder M. C., Ingram D. A. (2011). Differential mechanisms of x-ray-induced cell death in human endothelial progenitor cells isolated from cord blood and adults. Radiat. Res. 176, 208–216
    1. Michaud M., Martins I., Sukkurwala A. Q., Adjemian S., Ma Y., Pellegatti P., Shen S., Kepp O., Scoazec M., Mignot G., Rello-Varona S., Tailler M., Menger L., Vacchelli E., Galluzzi L., Ghiringhelli F., Di Virgilio F., Zitvogel L., Kroemer G. (2011). Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334, 1573–1577 10.1126/science.1208347
    1. Mole R. J. (1953). Whole body irradiation - radiology or medicine? Br. J. Radiol. 26, 234–241
    1. Munz C. (2009). Enhancing immunity through autophagy. Annu. Rev. Immunol. 27, 423–449 10.1146/annurev.immunol.021908.132537
    1. Nehs M. A., Lin C. I., Kozono D. E., Whang E. E., Cho N. L., Zhu K., Moalem J., Moore F. D., Jr., Ruan D. T. (2011). Necroptosis is a novel mechanism of radiation-induced cell death in anaplastic thyroid and adrenocortical cancers. Surgery 150, 1032–1039 10.1016/j.surg.2011.09.012
    1. Nobler M. P. (1969). The abscopal effect in malignant lymphoma and its relationship to lymphocyte circulation. Radiology 93, 410–412
    1. Obeid M., Panaretakis T., Joza N., Tufi R., Tesniere A., van Endert P., Zitvogel L., Kroemer G. (2007). Calreticulin exposure is required for the immunogenicity of gamma-irradiation and UVC light-induced apoptosis. Cell Death Differ. 14, 1848–1850 10.1038/sj.cdd.4402201
    1. Oda E., Ohki R., Murasawa H., Nemoto J., Shibue T., Yamashita T., Tokino T., Taniguchi T., Tanaka N. (2000). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288, 1053–1058 10.1126/science.288.5468.1053
    1. Ogura A., Oowada S., Kon Y., Hirayama A., Yasui H., Meike S., Kobayashi S., Kuwabara M., Inanami O. (2009). Redox regulation in radiation-induced cytochrome c release from mitochondria of human lung carcinoma A549 cells. Cancer Lett. 277, 64–71 10.1016/j.canlet.2008.11.021
    1. Ohba K., Omagari K., Nakamura T., Ikuno N., Saeki S., Matsuo I., Kinoshita H., Masuda J., Hazama H., Sakamoto I., Kohno S. (1998). Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis. Gut 43, 575–577
    1. Ohshima Y., Tsukimoto M., Takenouchi T., Harada H., Suzuki A., Sato M., Kitani H., Kojima S. (2010). gamma-Irradiation induces P2X(7) receptor-dependent ATP release from B16 melanoma cells. Biochim. Biophys. Acta 1800, 40–46 10.1016/j.bbagen.2009.10.008
    1. Orvedahl A., Levine B. (2009). Eating the enemy within: autophagy in infectious diseases. Cell Death Differ. 16, 57–69 10.1038/cdd.2008.130
    1. Paglin S., Hollister T., Delohery T., Hackett N., McMahill M., Sphicas E., Domingo D., Yahalom J. (2001). A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 61, 439–444
    1. Palumbo S., Comincini S. (2012). Autophagy and ionizing radiation in tumors: the “Survive or not Survive” dilemma. J. Cell. Physiol. [Epub ahead of print]. 10.1002/jcp.24118
    1. Panaretakis T., Kepp O., Brockmeier U., Tesniere A., Bjorklund A. C., Chapman D. C., Durchschlag M., Joza N., Pierron G., van Endert P., Yuan J., Zitvogel L., Madeo F., Williams D. B., Kroemer G. (2009). Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J. 28, 578–590 10.1038/emboj.2009.1
    1. Perez C. A., Fu A., Onishko H., Hallahan D. E., Geng L. (2009). Radiation induces an antitumour immune response to mouse melanoma. Int. J. Radiat. Biol. 85, 1126–1136 10.3109/09553000903242099
    1. Petrovski G., Ayna G., Majai G., Hodrea J., Benko S., Madi A., Fesus L. (2011). Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1beta release in human macrophages. Autophagy 7, 321–330 10.4161/auto.7.3.14583
    1. Quick Q. A., Gewirtz D. A. (2006). An accelerated senescence response to radiation in wild-type p53 glioblastoma multiforme cells. J. Neurosurg. 105, 111–118 10.3171/jns.2006.105.1.111
    1. Rodel F., Hoffmann J., Distel L., Herrmann M., Noisternig T., Papadopoulos T., Sauer R., Rodel C. (2005). Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res. 65, 4881–4887 10.1158/0008-5472.CAN-04-3028
    1. Rodriguez-Rocha H., Garcia-Garcia A., Panayiotidis M. I., Franco R. (2011). DNA damage and autophagy. Mutat. Res. 711, 158–166 10.1016/j.mrfmmm.2011.03.007
    1. Ruegg C., Monnier Y., Kuonen F., Imaizumi N. (2011). Radiation-induced modifications of the tumor microenvironment promote metastasis. Bull. Cancer 98, 47–57 10.1684/bdc.2011.1372
    1. Schultz L. B., Chehab N. H., Malikzay A., Halazonetis T. D. (2000). p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J. Cell Biol. 151, 1381–1390 10.1083/jcb.151.7.1381
    1. Sheard M. A. (2001). Ionizing radiation as a response-enhancing agent for CD95-mediated apoptosis. Int. J. Cancer 96, 213–220
    1. Shi Y., Venkataraman S. L., Dodson G. E., Mabb A. M., Leblanc S., Tibbetts R. S. (2004). Direct regulation of CREB transcriptional activity by ATM in response to genotoxic stress. Proc. Natl. Acad. Sci. U.S.A. 101, 5898–5903 10.1073/pnas.0307718101
    1. Shiraishi K., Ishiwata Y., Nakagawa K., Yokochi S., Taruki C., Akuta T., Ohtomo K., Matsushima K., Tamatani T., Kanegasaki S. (2008). Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1alpha. Clin. Cancer Res. 14, 1159–1166 10.1158/1078-0432.CCR-07-4485
    1. Siliciano J. D., Canman C. E., Taya Y., Sakaguchi K., Appella E., Kastan M. B. (1997). DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev. 11, 3471–3481 10.1101/gad.11.24.3471
    1. Siu A., Wind J. J., Iorgulescu J. B., Chan T. A., Yamada Y., Sherman J. H. (2012). Radiation necrosis following treatment of high grade glioma–a review of the literature and current understanding. Acta Neurochir. (Wien) 154, 191–201 discussion: 201. 10.1007/s00701-011-1228-6
    1. Smith J., Tho L. M., Xu N., Gillespie D. A. (2010). The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv. Cancer Res. 108, 73–112 10.1016/B978-0-12-380888-2.00003-0
    1. Stanger B. Z., Leder P., Lee T. H., Kim E., Seed B. (1995). RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81, 513–523 10.1016/0092-8674(95)90072-1
    1. Stewart R. D., Yu V. K., Georgakilas A. G., Koumenis C., Park J. H., Carlson D. J. (2011). Effects of radiation quality and oxygen on clustered DNA lesions and cell death. Radiat. Res. 176, 587–602
    1. Suzuki K., Mori I., Nakayama Y., Miyakoda M., Kodama S., Watanabe M. (2001). Radiation-induced senescence-like growth arrest requires TP53 function but not telomere shortening. Radiat. Res. 155, 248–253
    1. Takasawa R., Nakamura H., Mori T., Tanuma S. (2005). Differential apoptotic pathways in human keratinocyte HaCaT cells exposed to UVB and UVC. Apoptosis 10, 1121–1130 10.1007/s10495-005-0901-8
    1. Takaya M., Niibe Y., Tsunoda S., Jobo T., Imai M., Kotani S., Unno N., Hayakawa K. (2007). Abscopal effect of radiation on toruliform para-aortic lymph node metastases of advanced uterine cervical carcinoma–a case report. Anticancer Res. 27, 499–503
    1. Tang D., Loze M. T., Zeh H. J., Kang R. (2010). The redox protein HMGB1 regulates cell death and survival in cancer treatment. Autophagy 6, 1181–1183 10.4161/auto.6.8.13367
    1. Teng M. S., Futran N. D. (2005). Osteoradionecrosis of the mandible. Curr. Opin. Otolaryngol. Head Neck Surg. 13, 217–221
    1. Tesniere A., Schlemmer F., Boige V., Kepp O., Martins I., Ghiringhelli F., Aymeric L., Michaud M., Apetoh L., Barault L., Mendiboure J., Pignon J. P., Jooste V., van Endert P., Ducreux M., Zitvogel L., Piard F., Kroemer G. (2010). Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 29, 482–491 10.1038/onc.2009.356
    1. Tichy A., Zaskodova D., Zoelzer F., Vavrova J., Sinkorova Z., Pejchal J., Osterreicher J., Rezacova M. (2009). Gamma-radiation-induced phosphorylation of p53 on serine 15 is dose-dependent in MOLT-4 leukaemia cells. Folia Biol. (Praha) 55, 41–44
    1. Tsuchihara K., Fujii S., Esumi H. (2009). Autophagy and cancer: dynamism of the metabolism of tumor cells and tissues. Cancer Lett. 278, 130–138 10.1016/j.canlet.2008.09.040
    1. Vakifahmetoglu H., Olsson M., Tamm C., Heidari N., Orrenius S., Zhivotovsky B. (2008). DNA damage induces two distinct modes of cell death in ovarian carcinomas. Cell Death Differ. 15, 555–566 10.1038/sj.cdd.4402286
    1. Vanden Berghe T., van Loo G., Saelens X., van Gurp M., Brouckaert G., Kalai M., Declercq W., Vandenabeele P. (2004). Differential signaling to apoptotic and necrotic cell death by Fas-associated death domain protein FADD. J. Biol. Chem. 279, 7925–7933 10.1074/jbc.M307807200
    1. Vellai T., Takacs-Vellai K. (2010). Regulation of protein turnover by longevity pathways. Adv. Exp. Med. Biol. 694, 69–80
    1. Ventura A., Kirsch D. G., McLaughlin M. E., Tuveson D. A., Grimm J., Lintault L., Newman J., Reczek E. E., Weissleder R., Jacks T. (2007). Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661–665 10.1038/nature05541
    1. Vitale I., Galluzzi L., Castedo M., Kroemer G. (2011). Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat. Rev. Mol. Cell Biol. 12, 385–392 10.1038/nrm3115
    1. Vogel C., Hager C., Bastians H. (2007). Mechanisms of mitotic cell death induced by chemotherapy-mediated G2 checkpoint abrogation. Cancer Res. 67, 339–345 10.1158/0008-5472.CAN-06-2548
    1. Willingham S. B., Volkmer J. P., Gentles A. J., Sahoo D., Dalerba P., Mitra S. S., Wang J., Contreras-Trujillo H., Martin R., Cohen J. D., Lovelace P., Scheeren F. A., Chao M. P., Weiskopf K., Tang C., Volkmer A. K., Naik T. J., Storm T. A., Mosley A. R., Edris B., Schmid S. M., Sun C. K., Chua M. S., Murillo O., Rajendran P., Cha A. C., Chin R. K., Kim D., Adorno M., Raveh T., Tseng D., Jaiswal S., Enger P. O., Steinberg G. K., Li G., So S. K., Majeti R., Harsh G. R., van De Rijn M., Teng N. N., Sunwoo J. B., Alizadeh A. A., Clarke M. F., Weissman I. L. (2012). The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl. Acad. Sci. U.S.A. 109, 6662–6667 10.1073/pnas.1121623109
    1. Wu W. K., Coffelt S. B., Cho C. H., Wang X. J., Lee C. W., Chan F. K., Yu J., Sung J. J. (2012). The autophagic paradox in cancer therapy. Oncogene 31, 939–953
    1. Xue W., Zender L., Miething C., Dickins R. A., Hernando E., Krizhanovsky V., Cordon-Cardo C., Lowe S. W. (2007). Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 10.1038/nature05529
    1. Yao K. C., Komata T., Kondo Y., Kanzawa T., Kondo S., Germano I. M. (2003). Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. J. Neurosurg. 98, 378–384 10.3171/jns.2003.98.2.0378
    1. Zahnreich S., Melnikova L., Winter M., Nasonova E., Durante M., Ritter S., Fournier C. (2010). Radiation-induced premature senescence is associated with specific cytogenetic changes. Mutat. Res. 701, 60–66 10.1016/j.mrgentox.2010.03.010
    1. Zappasodi R., Pupa S. M., Ghedini G. C., Bongarzone I., Magni M., Cabras A. D., Colombo M. P., Carlo-Stella C., Gianni A. M., Di Nicola M. (2010). Improved clinical outcome in indolent B-cell lymphoma patients vaccinated with autologous tumor cells experiencing immunogenic death. Cancer Res. 70, 9062–9072 10.1158/0008-5472.CAN-10-1825
    1. Zitvogel L., Kepp O., Senovilla L., Menger L., Chaput N., Kroemer G. (2010). Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin. Cancer Res. 16, 3100–3104 10.1158/1078-0432.CCR-09-2891

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅