Degradation of tumour stromal hyaluronan by small extracellular vesicle-PH20 stimulates CD103⁺ dendritic cells and in combination with PD-L1 blockade boosts anti-tumour immunity

References

• Paulos CM, Kaiser A, Wrzesinski C, et al. Toll-like receptors in tumor immunotherapy. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5280–15. PubMed PMID: 17875756; PubMed Central PMCID: PMCPMC2131730.
   PubMed Web of Science ®Google Scholar
• Cen X, Liu S, Cheng K. The role of toll-like receptor in inflammation and tumor immunity. Front Pharmacol. 2018;9:878. PubMed PMID: 30127747; PubMed Central PMCID: PMCPMC6088210.
   Web of Science ®Google Scholar
• Krysko O, Love Aaes T, Bachert C, et al. Many faces of DAMPs in cancer therapy. Cell Death Dis. 2013 May 16;4:e631. PubMed PMID: 23681226; PubMed Central PMCID: PMCPMC3674363.
   PubMed Web of Science ®Google Scholar
• Piccinini AM, Midwood KS. DAMPening inflammation by modulating TLR signalling. Mediators Inflamm. 2010;2010. PubMed PMID: 20706656; PubMed Central PMCID: PMCPMC2913853. DOI:10.1155/2010/672395
   Web of Science ®Google Scholar
• Kelsh RM, McKeown-Longo PJ. Topographical changes in extracellular matrix: activation of TLR4 signaling and solid tumor progression. Trends Cancer Res. 2013 Jan 1;9:1–13. PubMed PMID: 24634571; PubMed Central PMCID: PMCPMC3952558.
   PubMedGoogle Scholar
• Fuchs K, Hippe A, Schmaus A, et al. Opposing effects of high- and low-molecular weight hyaluronan on CXCL12-induced CXCR4 signaling depend on CD44. Cell Death Dis. 2013 Oct 03;4:e819. PubMed PMID: 24091662; PubMed Central PMCID: PMCPMC3824673.
   PubMed Web of Science ®Google Scholar
• Cyphert JM, Trempus CS, Garantziotis S. Size matters: molecular weight specificity of hyaluronan effects in cell biology. Int J Cell Biol. 2015;2015:563818. PubMed PMID: 26448754; PubMed Central PMCID: PMC4581549.
   PubMedGoogle Scholar
• Murai T. Lipid raft-mediated regulation of hyaluronan-CD44 interactions in inflammation and cancer. Front Immunol. 2015;6:420. PubMed PMID: 26347743; PubMed Central PMCID: PMCPMC4542320.
   PubMed Web of Science ®Google Scholar
• Alaniz L, Garcia M, Rizzo M, et al. Altered hyaluronan biosynthesis and cancer progression: an immunological perspective. Mini Rev Med Chem. 2009 Nov 1;9(13):1538–1546. PubMed PMID: 20205635.
   Web of Science ®Google Scholar
• Kuang DM, Wu Y, Chen N, et al. Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes. Blood. 2007 Jul 15;110(2):587–595. PubMed PMID: 17395778.
   Web of Science ®Google Scholar
• Itano N, Zhuo L, Kimata K. Impact of the hyaluronan-rich tumor microenvironment on cancer initiation and progression. Cancer Sci. 2008 Sep;99(9):1720–1725. PubMed PMID: 18564137.
   PubMed Web of Science ®Google Scholar
• Wu RL, Huang L, Zhao HC, et al. Hyaluronic acid in digestive cancers. J Cancer Res Clin Oncol. 2017 Jan;143(1):1–16. 10.1007/s00432-016-2213-5. PubMed PMID: 27535565.
   Web of Science ®Google Scholar
• Alaniz L, Rizzo M, Garcia MG, et al. Low molecular weight hyaluronan preconditioning of tumor-pulsed dendritic cells increases their migratory ability and induces immunity against murine colorectal carcinoma. Cancer Immunol Immunother. 2011 Oct;60(10):1383–1395. PubMed PMID: 21638126.
   Web of Science ®Google Scholar
• Muto J, Morioka Y, Yamasaki K, et al. Hyaluronan digestion controls DC migration from the skin. J Clin Invest. 2014 Mar;124(3):1309–1319. PubMed PMID: 24487587; PubMed Central PMCID: PMC3934161.
   Web of Science ®Google Scholar
• Termeer C, Benedix F, Sleeman J, et al. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med. 2002 Jan 7;195(1):99–111. PubMed PMID: 11781369; PubMed Central PMCID: PMC2196009.
   PubMed Web of Science ®Google Scholar
• Olsson M, Bremer L, Aulin C, et al. Fragmented hyaluronan has no alarmin function assessed in arthritis synovial fibroblast and chondrocyte cultures. Innate Immun. 2018 Feb;24(2):131–141. PubMed PMID: 29495940.
   Web of Science ®Google Scholar
• Dong Y, Arif A, Olsson M, et al. Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-alpha, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages. Sci Rep. 2016 Nov 21;6:36928. PubMed PMID: 27869206; PubMed Central PMCID: PMCPMC5116629.
   Web of Science ®Google Scholar
• Ebid R, Lichtnekert J, Anders H-J. Hyaluronan is not a ligand but a regulator of toll-like receptor signaling in mesangial cells: role of extracellular matrix in innate immunity. ISRN Nephrol. 2014;2014:11.
   Google Scholar
• Hong Y, Nam G-H, Koh E, et al. Exosome as a vehicle for delivery of membrane protein therapeutics, PH20, for enhanced tumor penetration and antitumor efficacy. Adv Funct Mater. 2018;28(5):1703074.
   Web of Science ®Google Scholar
• Yang Y, Hong Y, Cho E, et al. Extracellular vesicles as a platform for membrane-associated therapeutic protein delivery. PubMed PMID: 29535849; PubMed Central PMCID: PMC5844050 J Extracell Vesicles. 2018;7(1):1440131.
   PubMed Web of Science ®Google Scholar
• Kultti A, Li X, Jiang P, et al. Therapeutic targeting of hyaluronan in the tumor stroma. Cancers (Basel). 2012 Sep 6;4(3):873–903. PubMed PMID: 24213471; PubMed Central PMCID: PMCPMC3712709.
   PubMedGoogle Scholar
• Provenzano PP, Cuevas C, Chang AE, et al. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012 Mar 20;21(3):418–429. PubMed PMID: 22439937; PubMed Central PMCID: PMC3371414.
   PubMed Web of Science ®Google Scholar
• Thompson CB, Shepard HM, O’Connor PM, et al. Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models. Mol Cancer Ther. 2010 Nov;9(11):3052–3064. PubMed PMID: 20978165.
   PubMed Web of Science ®Google Scholar
• Midura RJ, Cali V, Lauer ME, et al. Quantification of hyaluronan (HA) using a simplified fluorophore-assisted carbohydrate electrophoresis (FACE) procedure. Methods Cell Biol. 2018;143:297–316. PubMed PMID: 29310784.
   Web of Science ®Google Scholar
• Gao N. Fluorophore-assisted carbohydrate electrophoresis: a sensitive and accurate method for the direct analysis of dolichol pyrophosphate-linked oligosaccharides in cell cultures and tissues. Methods. 2005 Apr;35(4):323–327. PubMed PMID: 15804603.
   Web of Science ®Google Scholar
• Yang HZ, Cui B, Liu HZ, et al. Blocking TLR2 activity attenuates pulmonary metastases of tumor. PloS One. 2009 Aug 5;4(8):e6520. PubMed PMID: 19654875; PubMed Central PMCID: PMC2716531.
   PubMed Web of Science ®Google Scholar
• Toole BP. Hyaluronan-CD44 interactions in cancer: paradoxes and possibilities. Clin Cancer Res. 2009 Dec 15;15;(24):7462–7468. PubMed PMID: 20008845; PubMed Central PMCID: PMC2796593. Doi:10.1158/1078-0432.CCR-09-0479
   Web of Science ®Google Scholar
• Misra S, Hascall VC, Markwald RR, et al. Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer. Front Immunol. 2015;6:201. PubMed PMID: 25999946; PubMed Central PMCID: PMC4422082.
   PubMed Web of Science ®Google Scholar
• Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008 May;42(2):145–151. PubMed PMID: 18304834.
   PubMed Web of Science ®Google Scholar
• Kuzmich NN, Sivak KV, Chubarev VN, et al. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis. Vaccines (Basel). 2017 Oct 4;5(4). PubMed PMID: 28976923; PubMed Central PMCID: PMC5748601.
   PubMed Web of Science ®Google Scholar
• An H, Yu Y, Zhang M, et al. Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology. 2002 May;106(1):38–45. PubMed PMID: 11972630; PubMed Central PMCID: PMC1782697.
   Web of Science ®Google Scholar
• Fitzgerald KA, Rowe DC, Barnes BJ, et al. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med. 2003 Oct 6;198(7):1043–1055. PubMed PMID: 14517278; PubMed Central PMCID: PMC2194210.
   PubMed Web of Science ®Google Scholar
• Hubo M, Trinschek B, Kryczanowsky F, et al. Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells. Front Immunol. 2013;4:82. PubMed PMID: 23565116; PubMed Central PMCID: PMC3615188.
   PubMed Web of Science ®Google Scholar
• Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004 Oct;5(10):987–995. PubMed PMID: 15454922.
   PubMed Web of Science ®Google Scholar
• Jang MH, Sougawa N, Tanaka T, et al. CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes. J Immunol. 2006 Jan 15;176(2):803–810. PubMed PMID: 16393963.
   Web of Science ®Google Scholar
• Roberts EW, Broz ML, Binnewies M, et al. Critical role for CD103(+)/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in Melanoma. Cancer Cell. 2016 Aug 8;30(2):324–336. PubMed PMID: 27424807; PubMed Central PMCID: PMC5374862.
   PubMed Web of Science ®Google Scholar
• Hildner K, Edelson BT, Purtha WE, et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science. 2008 Nov 14;322(5904):1097–1100. PubMed PMID: 19008445; PubMed Central PMCID: PMC2756611.
   PubMed Web of Science ®Google Scholar
• Bollyky PL, Falk BA, Long SA, et al. CD44 costimulation promotes FoxP3+ regulatory T cell persistence and function via production of IL-2, IL-10, and TGF-beta. J Immunol. 2009 Aug 15;183(4):2232–2241. PubMed PMID: 19635906; PubMed Central PMCID: PMC3057032.
   Web of Science ®Google Scholar
• Rayahin JE, Buhrman JS, Zhang Y, et al. High and low molecular weight hyaluronic acid differentially influence macrophage activation. ACS Biomater Sci Eng. 2015 Jul 13;1(7):481–493. PubMed PMID: 26280020; PubMed Central PMCID: PMC4533115.
   PubMed Web of Science ®Google Scholar
• Mandai M, Hamanishi J, Abiko K, et al. Dual faces of IFNgamma in cancer progression: a role of PD-L1 induction in the determination of pro- and antitumor immunity. Clin Cancer Res. 2016 May 15;22(10):2329–2334. 10.1158/1078-0432.CCR-16-0224. PubMed PMID: 27016309.
   PubMed Web of Science ®Google Scholar
• Garcia-Diaz A, Shin DS, Moreno BH, et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 2017 May 9;19(6):1189–1201. PubMed PMID: 28494868.
   PubMed Web of Science ®Google Scholar
• Moynihan KD, Opel CF, Szeto GL, et al. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat Med. 2016 Dec;22(12):1402–1410. PubMed PMID: 27775706; PubMed Central PMCID: PMCPMC5209798.
   PubMed Web of Science ®Google Scholar
• Anderson KG, Stromnes IM, Greenberg PD. Obstacles posed by the tumor microenvironment to T cell activity: a case for synergistic therapies. Cancer Cell. 2017 Mar 13;31(3):311–325. PubMed PMID: 28292435; PubMed Central PMCID: PMCPMC5423788.
   PubMed Web of Science ®Google Scholar
• Jonkers J, Derksen PW. Modeling metastatic breast cancer in mice. J Mammary Gland Biol Neoplasia. 2007 Sep;12(2–3):191–203. PubMed PMID: 17587153.
   PubMed Web of Science ®Google Scholar
• Rodriguez LM, Guillén-Ponce C, Feliu J, et al. P-183 A pilot trial of PEGPH20 (pegvorhyaluronidase alfa) in combination with avelumab (anti-PD-L1 MSB0010718C) in chemotherapy resistant pancreatic cancer (PDAC)-trial in progress. Ann Oncol. 2018;29(suppl_5):mdy151.182.
   Google Scholar
• Thompson B, Kimbler T, Blouw B, et al. Abstract B38: increasing tumor-infiltrating CD8+ T cell response and checkpoint inhibitor efficacy by enzymatic reduction of tumor hyaluronan in a murine syngeneic pancreatic cancer model. Cancer Immunol Res. 2018;6(9 Supplement):B38–B38.
   Google Scholar
• Adachi K, Kano Y, Nagai T, et al. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018 Apr;36(4):346–351. PubMed PMID: 29505028.
   PubMed Web of Science ®Google Scholar
• Tang H, Wang Y, Chlewicki LK, et al. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell. 2016 Mar 14;29(3):285–296. PubMed PMID: 26977880; PubMed Central PMCID: PMCPMC4794755.
   PubMed Web of Science ®Google Scholar
• Bu X, Mahoney KM, Freeman GJ. Learning from PD-1 resistance: new combination strategies. Trends Mol Med. 2016 Jun;22(6):448–451. PubMed PMID: 27174038.
   PubMed Web of Science ®Google Scholar
• Tran TH, Mattheolabakis G, Aldawsari H, et al. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases. Clin Immunol. 2015 Sep;160(1):46–58. PubMed PMID: 25842185.
   Web of Science ®Google Scholar
• Zhang B, Yin Y, Lai RC, et al. Immunotherapeutic potential of extracellular vesicles. Front Immunol. 2014;5:518. PubMed PMID: 25374570; PubMed Central PMCID: PMC4205852.
   PubMed Web of Science ®Google Scholar
• Ingato D, Lee JU, Sim SJ, et al. Good things come in small packages: overcoming challenges to harness extracellular vesicles for therapeutic delivery. J Control Release. 2016 Nov 10;241:174–185. PubMed PMID: 27667180.
   PubMed Web of Science ®Google Scholar
• Syn NL, Wang L, Chow EK, et al. Exosomes in cancer nanomedicine and immunotherapy: prospects and challenges. Trends Biotechnol. 2017 Jul;35(7):665–676. PubMed PMID: 28365132.
   PubMed Web of Science ®Google Scholar
• Gilligan KE, Dwyer RM. Engineering exosomes for cancer therapy. Int J Mol Sci. 2017 May 24;18(6). PubMed PMID: 28538671; PubMed Central PMCID: PMCPMC5485946. DOI: 10.3390/ijms18061122
   PubMed Web of Science ®Google Scholar