A Stressful Microenvironment: Opposing Effects of the Endoplasmic Reticulum Stress Response in the Suppression and Enhancement of Adaptive Tumor Immunity

REFERENCES

• Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363:411–422.
   PubMed Web of Science ®Google Scholar
• Hodi FS, O apos Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–723.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Brahmer JR, Tykodi SS, Chow LQM, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455–2465.
   PubMed Web of Science ®Google Scholar
• Lipson EJ, Sharfman WH, Drake CG, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013;19:462–468.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122–133.
   PubMed Web of Science ®Google Scholar
• Dudley ME, Yang JC, Sherry R, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 2008;26:5233–5239.
   PubMed Web of Science ®Google Scholar
• Dudley ME, Gross CA, Langhan MM, et al. CD8+ enriched “young” tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin Cancer Res 2010;16:6122–6131.
   PubMed Web of Science ®Google Scholar
• Besser MJ, Shapira-Frommer R, Itzhaki O, et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin Cancer Res 2013;19:4792–4800.
   PubMed Web of Science ®Google Scholar
• Klebanoff CA, Acquavella N, Yu Z, et al. Therapeutic cancer vaccines: are we there yet? Immunol Rev 2011;239:27–44.
   PubMed Web of Science ®Google Scholar
• Prieto PA, Yang JC, Sherry RM, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 2012;18:2039–2047.
   PubMed Web of Science ®Google Scholar
• Kelderman S, Schumacher TNM, Haanen JBAG. Acquired and intrinsic resistance in cancer immunotherapy. Mol Oncol 2014;8:1132–1139.
   PubMed Web of Science ®Google Scholar
• Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883–899.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. The role of immune cells in the tumor microenvironment. Cancer Treat Res 2006;130:103–124.
   PubMedGoogle Scholar
• Fukumura D, Jain RK. Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem 2007;101:937–949.
   PubMed Web of Science ®Google Scholar
• Palazón A, Aragonés J, Morales-Kastresana A, et al. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res 2012;18:1207–1213.
   Google Scholar
• Clarke HJ, Chambers JE, Liniker E, et al. Endoplasmic reticulum stress in malignancy. Cancer Cell 2014;25:563–573.
   PubMed Web of Science ®Google Scholar
• Feldman DE. The unfolded protein response: a novel component of the hypoxic stress response in tumors. Mol Cancer Res 2005;3:597–605.
   PubMed Web of Science ®Google Scholar
• Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 2009;14:996–1007.
   PubMed Web of Science ®Google Scholar
• Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell 2006;125:443–451.
   PubMed Web of Science ®Google Scholar
• Chia WS, Chia DX, Rao F, et al. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain. Kursula I, editor. PLoS ONE 2012;7:e50490.
   Google Scholar
• Braakman I, Bulleid NJ. Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem 2011;80:71–99.
   PubMed Web of Science ®Google Scholar
• Oikawa D, Kimata Y, Kohno K, et al. Activation of mammalian IRE1alpha upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins. Exp Cell Res 2009;315:2496–2504.
   PubMed Web of Science ®Google Scholar
• Hirschberg CB, Robbins PW, Abeijon C. Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. Annu Rev Biochem 1998;67:49–69.
   PubMed Web of Science ®Google Scholar
• Le Gall S, Neuhof A, Rapoport T. The endoplasmic reticulum membrane is permeable to small molecules. Mol Biol Cell 2004;15:447–455.
   PubMed Web of Science ®Google Scholar
• Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 2014;14:581–597.
   PubMed Web of Science ®Google Scholar
• Kapoor A, Sanyal AJ. Endoplasmic reticulum stress and the unfolded protein response. Clin Liver Dis 2009;13:581–590.
   PubMed Web of Science ®Google Scholar
• Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011;334:1081–1086.
   PubMed Web of Science ®Google Scholar
• Rutkowski DT, Kaufman RJ. A trip to the ER: coping with stress. Trends Cell Biol 2004;14:20–28.
   PubMed Web of Science ®Google Scholar
• Schroder M, Kaufman RJ. ER stress and the unfolded protein response. Mutat Res 2005;569:29–63.
   PubMed Web of Science ®Google Scholar
• Wu J, Kaufman RJ. From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ 2006;13:374–384.
   PubMed Web of Science ®Google Scholar
• Ron D. Translational control in the endoplasmic reticulum stress response. J Clin Invest 2002;110:1383–1388.
   PubMed Web of Science ®Google Scholar
• Brewer JW, Diehl JA. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci 2000;97:12625–12630.
   PubMed Web of Science ®Google Scholar
• Yan W, Frank CL, Korth MJ, et al. Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc Natl Acad Sci U S A 2002;99:15920–15925.
   PubMed Web of Science ®Google Scholar
• Kaufman RJ, Scheuner D, Schroder M, et al. The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol 2002;3:411–421.
   PubMed Web of Science ®Google Scholar
• Harding HP, Zhang Y, Zeng H, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003;11:619–633.
   PubMed Web of Science ®Google Scholar
• Blais JD, Filipenko V, Bi M, et al. Activating transcription factor 4 is translationally regulated by hypoxic stress. Mol Cell Biol 2004;24:7469–7482.
   PubMed Web of Science ®Google Scholar
• Cullinan SB. PERK-dependent Activation of Nrf2 Contributes to Redox Homeostasis and Cell Survival following Endoplasmic Reticulum Stress. J Biol Chem 2004;279:20108–20117.
   PubMed Web of Science ®Google Scholar
• Cullinan SB, Zhang D, Hannink M, et al. Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol 2003;23:7198–7209.
   PubMed Web of Science ®Google Scholar
• Bi M, Naczki C, Koritzinsky M, et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. Embo J 2005;24:3470–3481.
   PubMed Web of Science ®Google Scholar
• Koumenis C, Naczki C, Koritzinsky M, et al. Regulation of Protein Synthesis by Hypoxia via Activation of the Endoplasmic Reticulum Kinase PERK and Phosphorylation of the Translation Initiation Factor eIF2. Mol Cell Biol 2002;22:7405–7416.
   PubMed Web of Science ®Google Scholar
• Ye J, Kumanova M, Hart LS, et al. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. Embo J 2010;29:2082–2096.
   PubMed Web of Science ®Google Scholar
• Rouschop KMA, van den Beucken T, Dubois L, et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest 2010;120:127–141.
   PubMed Web of Science ®Google Scholar
• Mujcic H, Nagelkerke A, Rouschop KMA, et al. Hypoxic activation of the PERK/eIF2α arm of the unfolded protein response promotes metastasis through induction of LAMP3. Clin Cancer Res 2013;19:6126–6137.
   PubMed Web of Science ®Google Scholar
• Nagelkerke A, Bussink J, Mujcic H, et al. Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response. Breast Cancer Res 2013;15:R2.
   PubMed Web of Science ®Google Scholar
• Rzymski T, Milani M, Pike L, et al. Regulation of autophagy by ATF4 in response to severe hypoxia. Oncogene 2010;29:4424–4435.
   PubMed Web of Science ®Google Scholar
• Harding HP, Calfon M, Urano F, et al. Transcriptional and translational control in the Mammalian unfolded protein response. Annu Rev Cell Dev Biol 2002;18:575–599.
   PubMed Web of Science ®Google Scholar
• Calfon M, Zeng H, Urano F, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 2002;415:92–96.
   PubMed Web of Science ®Google Scholar
• Lee K, Tirasophon W, Shen X, et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 2002;16:452–466.
   PubMed Web of Science ®Google Scholar
• Lin JH, Li H, Yasumura D, et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 2007;318:944–949.
   PubMed Web of Science ®Google Scholar
• Romero-Ramirez L, Cao H, Nelson D, et al. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res 2004;64:5943–5947.
   PubMed Web of Science ®Google Scholar
• Shen J, Prywes R. ER stress signaling by regulated proteolysis of ATF6. Methods 2005;35:382–389.
   PubMedGoogle Scholar
• Shen J, Snapp EL, Lippincott-Schwartz J, et al. Stable Binding of ATF6 to BiP in the Endoplasmic Reticulum Stress Response. Mol Cell Biol 2005;25:921–932.
   PubMedGoogle Scholar
• Shen J, Chen X, Hendershot L, et al. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Developmental Cell 2002;3:99–111.
   PubMed Web of Science ®Google Scholar
• Wang Y, Shen J, Arenzana N, et al. Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. J Biol Chem 2000;275:27013–27020.
   PubMed Web of Science ®Google Scholar
• Yamamoto K, Yoshida H, Kokame K, et al. Differential contributions of ATF6 and XBP1 to the activation of endoplasmic reticulum stress-responsive cis-acting elements ERSE, UPRE and ERSE-II. J Biochem 2004;136:343–350.
   PubMed Web of Science ®Google Scholar
• Wu J, Rutkowski DT, Dubois M, et al. ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Developmental Cell 2007;13: 351–364.
   PubMed Web of Science ®Google Scholar
• Song MS, Park YK, Lee JH, et al. Induction of glucose-regulated protein 78 by chronic hypoxia in human gastric tumor cells through a protein kinase C-epsilon/ERK/AP-1 signaling cascade. Cancer Res 2001;61:8322–8330.
   PubMed Web of Science ®Google Scholar
• Gazit G, Lu J, Lee AS. De-regulation of GRP stress protein expression in human breast cancer cell lines. Breast Cancer Res Treat 1999;54:135–146.
   PubMed Web of Science ®Google Scholar
• Luo B, Lee AS. The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies. Oncogene 2013;32:805–818.
   PubMed Web of Science ®Google Scholar
• Jamora C, Dennert G, Lee AS. Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME. Proc Natl Acad Sci U S A 1996;93:7690–7694.
   PubMed Web of Science ®Google Scholar
• Li Z, Li Z. Glucose regulated protein 78: a critical link between tumor microenvironment and cancer hallmarks. Biochim Biophys Acta 2012;1826:13–22.
   PubMed Web of Science ®Google Scholar
• Koong AC, Auger EA, Chen EY, et al. The regulation of GRP78 and messenger RNA levels by hypoxia is modulated by protein kinase C activators and inhibitors. Radiat Res 1994;138:S60–S63.
   PubMedGoogle Scholar
• Reddy RK, Mao C, Baumeister P, et al. Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem 2003;278:20915–20924.
   PubMed Web of Science ®Google Scholar
• Dong D, Ko B, Baumeister P, et al. Vascular targeting and antiangiogenesis agents induce drug resistance effector GRP78 within the tumor microenvironment. Cancer Res 2005;65:5785–5791.
   PubMed Web of Science ®Google Scholar
• Lee E, Nichols P, Spicer D, et al. GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer. Cancer Res 2006;66:7849–7853.
   PubMed Web of Science ®Google Scholar
• Kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest 2002;110:1389–1398.
   PubMed Web of Science ®Google Scholar
• Ranganathan AC, Zhang L, Adam AP, et al. Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells. Cancer Res 2006;66:1702–1711.
   PubMed Web of Science ®Google Scholar
• Ranganathan AC, Adam AP, Zhang L, et al. Tumor cell dormancy induced by p38SAPK and ER-stress signaling: an adaptive advantage for metastatic cells? Cancer Biol Ther 2006;5: 729–735.
   PubMed Web of Science ®Google Scholar
• Zhou H, Zhang Y, Fu Y, et al. Novel mechanism of anti-apoptotic function of 78-kDa glucose-regulated protein (GRP78): endocrine resistance factor in breast cancer, through release of B-cell lymphoma 2 (BCL-2) from BCL-2-interacting killer (BIK). J Biol Chem 2011;286:25687–25696.
   PubMed Web of Science ®Google Scholar
• Fu Y, Lee AS. Glucose regulated proteins in cancer progression, drug resistance and immunotherapy. Cancer Biol Ther 2006;5:741–744.
   PubMed Web of Science ®Google Scholar
• Kanao H, Enomoto T, Kimura T, et al. Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer. Cancer Res 2005;65:8640–8645.
   PubMed Web of Science ®Google Scholar
• Nagelkerke A, Mujcic H, Bussink J, et al. Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer. Cancer 2011;117:3670–3681.
   Google Scholar
• Nagelkerke A, Sweep FCGJ, Stegeman H, et al. Hypoxic regulation of the PERK/ATF4/LAMP3-arm of the unfolded protein response in head and neck squamous cell carcinoma. Head Neck 2014;doi:10.1002/hed.23693. [Epub ahead of print].
   Google Scholar
• Nagelkerke A, Sieuwerts AM, Bussink J, et al. LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy. Endocr Relat Cancer 2014;21:101–112.
   PubMed Web of Science ®Google Scholar
• Nagelkerke A, Bussink J, van der Kogel AJ, et al. The PERK/ATF4/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response. Radiother Oncol 2013;108:415–421.
   PubMed Web of Science ®Google Scholar
• Ranganathan AC, Ojha S, Kourtidis A, et al. Dual function of pancreatic endoplasmic reticulum kinase in tumor cell growth arrest and survival. Cancer Res 2008;68:3260–3268.
   PubMed Web of Science ®Google Scholar
• Atkins C, Liu Q, Minthorn E, et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 2013;73:1993–2002.
   PubMed Web of Science ®Google Scholar
• Tang C-HA, Ranatunga S, Kriss CL, et al. Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival. J Clin Invest 2014;124:2585–2598.
   PubMed Web of Science ®Google Scholar
• Papandreou I, Denko NC, Olson M. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 2011;117:1311–1314.
   PubMed Web of Science ®Google Scholar
• Higa A, Taouji S, Lhomond S, et al. Endoplasmic reticulum stress-activated transcription factor ATF6α requires the disulfide isomerase PDIA5 to modulate chemoresistance. Mol Cell Biol 2014;34:1839–1849.
   PubMed Web of Science ®Google Scholar
• Schewe DM, Aguirre-Ghiso JA. ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc Natl Acad Sci 2008;105:10519–10524.
   PubMed Web of Science ®Google Scholar
• Rutkowski DT, Arnold SM, Miller CN, et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. Plos Biol 2006;4:e374.
   PubMed Web of Science ®Google Scholar
• Ohoka N, Yoshii S, Hattori T, et al. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J 2005;24:1243–1255.
   PubMed Web of Science ®Google Scholar
• Urano F, Wang X, Bertolotti A, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000;287:664–666.
   PubMed Web of Science ®Google Scholar
• Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nature Cell Biology 2011;13:184–190.
   PubMed Web of Science ®Google Scholar
• Deng J, Lu PD, Zhang Y, et al. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol Cell Biol 2004;24:10161–10168.
   PubMed Web of Science ®Google Scholar
• Kaneko M, Niinuma Y, Nomura Y. Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2. Biol Pharm Bull 2003;26:931–935.
   PubMed Web of Science ®Google Scholar
• Yamazaki H, Hiramatsu N, Hayakawa K, et al. Activation of the Akt-NF-kappaB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol 2009;183:1480–1487.
   PubMed Web of Science ®Google Scholar
• Garg AD, Kaczmarek A, Krysko O, et al. ER stress-induced inflammation: does it aid or impede disease progression? Trends Mol Med 2012;18:589–598.
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 2008;8:923–934.
   PubMed Web of Science ®Google Scholar
• Zhang K, Shen X, Wu J, et al. Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell 2006;124:587–599.
   PubMed Web of Science ®Google Scholar
• Gurzov EN, Ortis F, Cunha DA, et al. Signaling by IL-1beta+IFN-gamma and ER stress converge on DP5/Hrk activation: a novel mechanism for pancreatic beta-cell apoptosis. Cell Death Differ 2009;16:1539–1550.
   PubMed Web of Science ®Google Scholar
• Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature 2008;454:455–462.
   PubMed Web of Science ®Google Scholar
• Liu Y-P, Zeng L, Tian A, et al. Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3. J Immunol 2012;189:4630–4639.
   PubMed Web of Science ®Google Scholar
• Zeng L, Liu Y-P, Sha H, et al. XBP-1 couples endoplasmic reticulum stress to augmented IFN-beta induction via a cis-acting enhancer in macrophages. J Immunol 2010;185:2324–2330.
   PubMedGoogle Scholar
• Hu F, Yu X, Wang H, et al. ER stress and its regulator X-box-binding protein-1 enhance polyIC-induced innate immune response in dendritic cells. Eur J Immunol 2011;41:1086–1097.
   PubMed Web of Science ®Google Scholar
• Muralidharan S, Mandrekar P. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 2013;94:1167–1184.
   PubMed Web of Science ®Google Scholar
• Smith JA. A new paradigm: innate immune sensing of viruses via the unfolded protein response. Front Microbiol 2014;5:222.
   PubMed Web of Science ®Google Scholar
• Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature 2006;442:461–465.
   PubMed Web of Science ®Google Scholar
• Qian X, Gu L, Ning H, et al. Increased Th17 cells in the tumor microenvironment is mediated by IL-23 via tumor-secreted prostaglandin E2. J Immunol 2013;190:5894–5902.
   PubMed Web of Science ®Google Scholar
• Jensen PE. Recent advances in antigen processing and presentation. Nat Immunol 2007;8:1041–1048.
   PubMed Web of Science ®Google Scholar
• Vyas JM, Van der Veen AG, Ploegh HL. The known unknowns of antigen processing and presentation. Nat Rev Immunol 2008;8:607–618.
   PubMed Web of Science ®Google Scholar
• Granados DP, Tanguay P-L, Hardy M-P, et al. ER stress affects processing of MHC class I-associated peptides. BMC Immunol 2009;10:10.
   PubMed Web of Science ®Google Scholar
• de Almeida SF, Fleming JV, Azevedo JE, et al. Stimulation of an unfolded protein response impairs MHC class I expression. J Immunol 2007;178:3612–3619.
   Google Scholar
• de Almeida SF, Carvalho IF, Cardoso CS, et al. HFE cross-talks with the MHC class I antigen presentation pathway. Blood 2005;106:971–977.
   PubMed Web of Science ®Google Scholar
• Shaikh SR, Mitchell D, Carroll E, et al. Differential effects of a saturated and a monounsaturated fatty acid on MHC class I antigen presentation. Scand J Immunol 2008;68:30–42.
   Google Scholar
• Pellicciotta I, Cortez-Gonzalez X, Sasik R, et al. Presentation of telomerase reverse transcriptase, a self-tumor antigen, is down-regulated by histone deacetylase inhibition. Cancer Res 2008;68:8085–8093.
   PubMed Web of Science ®Google Scholar
• Cabrera CM. The double role of the endoplasmic reticulum chaperone tapasin in peptide optimization of HLA class I molecules. Scand J Immunol 2007;65:487–493.
   PubMed Web of Science ®Google Scholar
• Kaufman RJ. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 1999;13:1211–1233.
   PubMed Web of Science ®Google Scholar
• Wheeler MC, Rizzi M, Sasik R, et al. KDEL-retained antigen in B lymphocytes induces a proinflammatory response: a possible role for endoplasmic reticulum stress in adaptive T cell immunity. J Immunol 2008;181:256–264.
   PubMedGoogle Scholar
• Bartoszewski R, Brewer JW, Rab A, et al. The unfolded protein response (UPR)-activated transcription factor X-box-binding protein 1 (XBP1) induces microRNA-346 expression that targets the human antigen peptide transporter 1 (TAP1) mRNA and governs immune regulatory genes. J Biol Chem 2011;286:41862–41870.
   PubMed Web of Science ®Google Scholar
• Ostankovitch M, Robila V, Engelhard VH. Regulated folding of tyrosinase in the endoplasmic reticulum demonstrates that misfolded full-length proteins are efficient substrates for class I processing and presentation. J Immunol 2005;174:2544–2551.
   PubMed Web of Science ®Google Scholar
• Schwab SR, Shugart JA, Horng T, et al. Unanticipated antigens: translation initiation at CUG with leucine. Plos Biol 2004;2:e366.
   PubMed Web of Science ®Google Scholar
• Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 2011;469:323–335.
   PubMed Web of Science ®Google Scholar
• Münz C. Antigen processing via autophagy–not only for MHC class II presentation anymore? Curr Opin Immunol 2010;22:89–93.
   PubMed Web of Science ®Google Scholar
• Viry E, Paggetti J, Baginska J, et al. Autophagy: An adaptive metabolic response to stress shaping the antitumor immunity. Biochem Pharmacol 2014;92:31–42.
   PubMed Web of Science ®Google Scholar
• Yorimitsu T, Nair U, Yang Z, et al. Endoplasmic reticulum stress triggers autophagy. J Biol Chem 2006;281:30299–30304.
   PubMed Web of Science ®Google Scholar
• Kawakami T, Inagi R, Takano H, et al. Endoplasmic reticulum stress induces autophagy in renal proximal tubular cells. Nephrol Dial Transplant 2009;24:2665–2672.
   PubMed Web of Science ®Google Scholar
• Fiegl D, Kägebein D, Liebler-Tenorio EM, et al. Amphisomal route of MHC class I cross-presentation in bacteria-infected dendritic cells. J Immunol 2013;190:2791–2806.
   PubMed Web of Science ®Google Scholar
• Li Y, Wang L-X, Yang G, et al. Efficient cross-presentation depends on autophagy in tumor cells. Cancer Res 2008;68:6889–6895.
   PubMed Web of Science ®Google Scholar
• Dengjel J, Schoor O, Fischer R, et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci 2005;102:7922–7927.
   PubMed Web of Science ®Google Scholar
• Noman MZ, Buart S, Van Pelt J, et al. The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis. J Immunol 2009;182:3510–3521.
   PubMed Web of Science ®Google Scholar
• Noman MZ, Janji B, Kaminska B, et al. Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression. Cancer Res 2011;71:5976–5986.
   PubMed Web of Science ®Google Scholar
• Krysko DV, Garg AD, Kaczmarek A, et al. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012;12:860–875.
   PubMed Web of Science ®Google Scholar
• Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 2007;13:54–61.
   PubMed Web of Science ®Google Scholar
• De Boo S, Kopecka J, Brusa D, et al. iNOS activity is necessary for the cytotoxic and immunogenic effects of doxorubicin in human colon cancer cells. Mol Cancer 2009;8:108.
   PubMed Web of Science ®Google Scholar
• Panaretakis T, Kepp O, Brockmeier U, et al. Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J 2009;28:578–590.
   PubMed Web of Science ®Google Scholar
• Tesnière A, Schlemmer F, Boige V, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 2010;29:482–491.
   PubMed Web of Science ®Google Scholar
• Garg AD, Krysko DV, Verfaillie T, et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J 2012;31:1062–1079.
   PubMed Web of Science ®Google Scholar
• Qin Y, Han Y, Cao C, et al. Melanoma B16-F1 cells coated with fusion protein of mouse calreticulin and virus G-protein coupled receptor induced the antitumor immune response in Balb/C mice. Cancer Biol Ther 2011;11:574–580.
   PubMed Web of Science ®Google Scholar
• Senovilla L, Vitale I, Martins I, et al. An immunosurveillance mechanism controls cancer cell ploidy. Science 2012;337:1678–1684.
   PubMed Web of Science ®Google Scholar
• Gardai SJ, McPhillips KA, Frasch SC, et al. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 2005;123: 321–334.
   PubMed Web of Science ®Google Scholar
• Peters LR, Raghavan M. Endoplasmic reticulum calcium depletion impacts chaperone secretion, innate immunity, and phagocytic uptake of cells. J Immunol 2011;187:919–931.
   Google Scholar
• Pawaria S, Binder RJ. CD91-dependent programming of T-helper cell responses following heat shock protein immunization. Nat Commun 2011;2:521.
   PubMed Web of Science ®Google Scholar
• Wilke CM, Kryczek I, Wei S, et al. Th17 cells in cancer: help or hindrance? Carcinogenesis 2011;32:643–649.
   PubMed Web of Science ®Google Scholar
• Wilke CM, Kryczek I, Wei S, et al. Th17 cells in cancer: help or hindrance? Carcinogenesis 2011;32:643–649.
   PubMed Web of Science ®Google Scholar
• Alizadeh D, Katsanis E, Larmonier N. The multifaceted role of Th17 lymphocytes and their associated cytokines in cancer. Clin Dev Immunol 2013;2013:957878–957811.
   Google Scholar
• Garg AD, Dudek AM, Agostinis P. Calreticulin surface exposure is abrogated in cells lacking, chaperone-mediated autophagy-essential gene, LAMP2A. Cell Death Dis 2013;4:e826.
   Google Scholar
• Elliott MR, Chekeni FB, Trampont PC, et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009;461:282–286.
   PubMed Web of Science ®Google Scholar
• Michaud M, Martins I, Sukkurwala AQ, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011;334:1573–1577.
   PubMed Web of Science ®Google Scholar
• Wemeau M, Kepp O, Tesnière A, et al. Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia. Cell Death Dis 2010;1:e104.
   PubMed Web of Science ®Google Scholar
• Zappasodi R, Pupa SM, Ghedini GC, et al. Improved clinical outcome in indolent B-cell lymphoma patients vaccinated with autologous tumor cells experiencing immunogenic death. Cancer Res 2010;70:9062–9072.
   PubMed Web of Science ®Google Scholar
• Peng R-Q, Chen Y-B, Ding Y, et al. Expression of calreticulin is associated with infiltration of T-cells in stage IIIB colon cancer. World J Gastroenterol 2010;16:2428–2434.
   PubMed Web of Science ®Google Scholar
• Ni M, Zhang Y, Lee AS. Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem J 2011;434:181–188.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Gronow M, Cuchacovich M, Llanos C, et al. Prostate cancer cell proliferation in vitro is modulated by antibodies against glucose-regulated protein 78 isolated from patient serum. Cancer Res 2006;66:11424–11431.
   PubMed Web of Science ®Google Scholar
• Shani G, Fischer WH, Justice NJ, et al. GRP78 and Cripto form a complex at the cell surface and collaborate to inhibit transforming growth factor beta signaling and enhance cell growth. Mol Cell Biol 2008;28:666–677.
   PubMed Web of Science ®Google Scholar
• Oida T, Weiner HL. Overexpression of TGF-ß 1 gene induces cell surface localized glucose-regulated protein 78-associated latency-associated peptide/TGF-ß. J Immunol 2010;185:3529–3535.
   PubMed Web of Science ®Google Scholar
• Corrigall VM, Vittecoq O, Panayi GS. Binding immunoglobulin protein-treated peripheral blood monocyte-derived dendritic cells are refractory to maturation and induce regulatory T-cell development. Immunology 2009;128:218–226.
   PubMed Web of Science ®Google Scholar
• Oresic K, Tortorella D. Endoplasmic reticulum chaperones participate in human cytomegalovirus US2-mediated degradation of class I major histocompatibility complex molecules. J Gen Virol 2008;89:1122–1130.
   Google Scholar
• Paulsson KM, Wang P, Anderson PO, et al. Distinct differences in association of MHC class I with endoplasmic reticulum proteins in wild-type, and beta 2-microglobulin- and TAP-deficient cell lines. Int Immunol 2001;13:1063–1073.
   Google Scholar
• Triantafilou K, Fradelizi D, Wilson K, et al. GRP78, a coreceptor for coxsackievirus A9, interacts with major histocompatibility complex class I molecules which mediate virus internalization. J Virol 2002;76:633–643.
   PubMed Web of Science ®Google Scholar
• Misra UK, Gonzalez-Gronow M, Gawdi G, et al. The role of MTJ-1 in cell surface translocation of GRP78, a receptor for alpha 2-macroglobulin-dependent signaling. J Immunol 2005;174:2092–2097.
   PubMed Web of Science ®Google Scholar
• Srivastava P. Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2002;2:185–194.
   PubMed Web of Science ®Google Scholar
• Srivastava PK, DeLeo AB, Old LJ. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci U S A 1986;83:3407–3411.
   PubMed Web of Science ®Google Scholar
• Basu S, Binder RJ, Ramalingam T, et al. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 2001;14:303–313.
   PubMed Web of Science ®Google Scholar
• Calderwood SK, Mambula SS, Gray PJ. Extracellular heat shock proteins in cell signaling and immunity. Ann N Y Acad Sci 2007;1113:28–39.
   PubMed Web of Science ®Google Scholar
• Podack ER, Raez LE. Allogeneic tumor-cell-based vaccines secreting endoplasmic reticulum chaperone gp96. Expert Opin Biol Ther 2007;7:1679–1688.
   PubMed Web of Science ®Google Scholar
• Chinni SR, Falchetto R, Gercel-Taylor C, et al. Humoral immune responses to cathepsin D and glucose-regulated protein 78 in ovarian cancer patients. Clin Cancer Res 1997;3:1557–1564.
   Google Scholar
• Mintz PJ, Kim J, Do K-A, et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol 2003;21:57–63.
   PubMed Web of Science ®Google Scholar
• Rauschert N, Brändlein S, Holzinger E, et al. A new tumor-specific variant of GRP78 as target for antibody-based therapy. Lab Invest 2008;88:375–386.
   PubMed Web of Science ®Google Scholar