Journal of Zhejiang University-SCIENCE B

, Volume 21, Issue 1, pp 3–11 | Cite as

Lymphatic vasculature in tumor metastasis and immunobiology

  • Xinguo JiangEmail author


Lymphatic vessels are essential for tissue fluid homeostasis, immune cell trafficking, and intestinal lipid absorption. The lymphatics have long been recognized to serve as conduits for distant tumor dissemination. However, recent findings suggest that the regional lymphatic vasculature also shapes the immune microenvironment of the tumor mass and potentiates immunotherapy. This review discusses the role of lymphatic vessels in tumor metastasis and tumor immunity.

Key words

Lymphatic Lymphatic endothelial cell (LEC) Cancer Metastasis Immunotherapy 



淋巴系统被认为是肿瘤转移的重要途径之一, 所以通常情况下肿瘤引起的淋巴血管增生会降低肿瘤预后, 治疗上也建议淋巴清扫。 但是最新的研究显示, 淋巴系统可能对肿瘤免疫治疗有促进作用. 这篇综述的主要目的是对相关领域做一个简短总结, 以期待将来有更多的研究来关注淋巴系统对肿瘤治疗的影响. 文章首先介绍肿瘤淋巴血管增生和淋巴转移的分子机制, 然后介绍淋巴系统在肿瘤免疫中的作用, 最后利用最新研究来证明淋巴系统有增强肿瘤免疫治疗的作用.


淋巴系统 淋巴内皮细胞 肿瘤 转移 免疫治疗 

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The author wishes to gratefully acknowledge Dr. Stanley ROCKSON (Stanford University, USA) for critical comments on this manuscript.

Compliance with ethics guidelines

Xinguo JIANG declares that he has no conflict of interest.

This article does not contain any studies with human or animal subjects performed by the author.


  1. Allen F, Rauhe P, Askew D, et al., 2017. CCL3 enhances antitumor immune priming in the lymph node via IFNγ with dependency on natural killer cells. Front Immunol, 8:1390. PubMedPubMedCentralGoogle Scholar
  2. Arbiser JL, Moses MA, Fernandez CA, et al., 1997. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA, 94(3):861–866. PubMedGoogle Scholar
  3. Ariffin AB, Forde PF, Jahangeer S, et al., 2014. Releasing pressure in tumors: what do we know so far and where do we go from here? A review. Cancer Res, 74(10):2655–2662. PubMedGoogle Scholar
  4. Aspelund A, Robciuc MR, Karaman S, et al., 2016. Lymphatic system in cardiovascular medicine. Circul Res, 118(3): 515–530. Google Scholar
  5. Baluk P, Fuxe J, Hashizume H, et al., 2007. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med, 204(10):2349–2362. PubMedPubMedCentralGoogle Scholar
  6. Baluk P, Yao LC, Feng J, et al., 2009. TNF-α drives remodeling of blood vessels and lymphatics in sustained airway inflammation in mice. J Clin Invest, 119(10):2954–2964. PubMedPubMedCentralGoogle Scholar
  7. Baluk P, Hogmalm A, Bry M, et al., 2013. Transgenic overexpression of interleukin-1β induces persistent lymphangiogenesis but not angiogenesis in mouse airways. Am J Pathol, 182(4):1434–1447. PubMedPubMedCentralGoogle Scholar
  8. Boardman KC, Swartz MA, 2003. Interstitial flow as a guide for lymphangiogenesis. Circul Res, 92(7):801–808. Google Scholar
  9. Bordry N, Broggi MAS, de Jonge K, et al., 2018. Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma. Oncoimmunology, 7(8):e1462878. PubMedPubMedCentralGoogle Scholar
  10. Cao YH, 2005. Emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nat Rev Cancer, 5(9): 735–743. PubMedGoogle Scholar
  11. Card CM, Yu SS, Swartz MA, 2014. Emerging roles of lymphatic endothelium in regulating adaptive immunity. J Clin Invest, 124(3):943–952. PubMedPubMedCentralGoogle Scholar
  12. Chandrasekaran S, King MR, 2014. Microenvironment of tumor-draining lymph nodes: opportunities for liposome-based targeted therapy. Int J Mol Sci, 15(11):20209–20239. PubMedPubMedCentralGoogle Scholar
  13. Chen DS, Mellman I, 2017. Elements of cancer immunity and the cancer-immune set point. Nature, 541(7637):321–330. PubMedPubMedCentralGoogle Scholar
  14. Christiansen AJ, Dieterich LC, Ohs I, et al., 2016. Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation. Oncotarget, 7(26):39421–39435. PubMedPubMedCentralGoogle Scholar
  15. Cui Y, Liu K, Lamattina AM, et al., 2017. Lymphatic vessels: the next frontier in lung transplant. Ann Am Thorac Soc, 14(S3):S226–S232. PubMedPubMedCentralGoogle Scholar
  16. da Mesquita S, Louveau A, Vaccari A, et al., 2018. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature, 560(7717):185–191. PubMedPubMedCentralGoogle Scholar
  17. Dadras SS, Paul T, Bertoncini J, et al., 2003. Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol, 162(6):1951–1960. PubMedPubMedCentralGoogle Scholar
  18. Das S, Sarrou E, Podgrabinska S, et al., 2013. Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. J Exp Med, 210(8):1509–1528. PubMedPubMedCentralGoogle Scholar
  19. Dieterich LC, Ikenberg K, Cetintas T, et al., 2017. Tumor-associated lymphatic vessels upregulate PDL1 to inhibit T-cell activation. Front Immunol, 8:66. PubMedPubMedCentralGoogle Scholar
  20. Enholm B, Paavonen K, Ristimaki A, et al., 1997. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene, 14(20):2475–2483. PubMedGoogle Scholar
  21. Fankhauser M, Broggi MAS, Potin L, et al., 2017. Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma. Sci Transl Med, 9(407):eaal4712. PubMedGoogle Scholar
  22. Folkman J, 1971. Tumor angiogenesis: therapeutic implications. N Engl J Med, 285(21):1182–1186. PubMedGoogle Scholar
  23. Förster R, Davalos-Misslitz AC, Rot A, 2008. CCR7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol, 8(5):362–371. PubMedPubMedCentralGoogle Scholar
  24. Fransen MF, Schoonderwoerd M, Knopf P, et al., 2018. Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. JCI Insight, 3(23):e124507. PubMedCentralGoogle Scholar
  25. Gao P, Li CJ, Chang Z, et al., 2018. Carcinoma associated fibroblasts derived from oral squamous cell carcinoma promote lymphangiogenesis via c-Met/PI3K/AKT in vitro. Oncol Lett, 15(1):331–337. PubMedGoogle Scholar
  26. Guan XM, 2015. Cancer metastases: challenges and opportunities. Acta Pharm Sin B, 5(5):402–418. PubMedPubMedCentralGoogle Scholar
  27. Harris AR, Perez MJ, Munson JM, 2018. Docetaxel facilitates lymphatic-tumor crosstalk to promote lymphangiogenesis and cancer progression. BMC Cancer, 18:718. PubMedPubMedCentralGoogle Scholar
  28. Harvey NL, Gordon EJ, 2012. Deciphering the roles of macrophages in developmental and inflammation stimulated lymphangiogenesis. Vascular Cell, 4(1):15. PubMedPubMedCentralGoogle Scholar
  29. Henri O, Pouehe C, Houssari M, et al., 2016. Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction. Circulation, 133(15): 1484–1497. PubMedGoogle Scholar
  30. Hirakawa S, Kodama S, Kunstfeld R, et al., 2005. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med, 201(7):1089–1099. PubMedPubMedCentralGoogle Scholar
  31. Hirakawa S, Brown LF, Kodama S, et al., 2007. VEGF-Cinduced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood, 109(3): 1010–1017. PubMedPubMedCentralGoogle Scholar
  32. Hirakawa S, Detmar M, Kerjaschki D, et al., 2009. Nodal lymphangiogenesis and metastasis: role of tumor-induced lymphatic vessel activation in extramammary Paget’s disease. Am J Pathol, 175(5):2235–2248. PubMedPubMedCentralGoogle Scholar
  33. Hos D, Cursiefen C, 2014. Lymphatic vessels in the development of tissue and organ rejection. In: Kiefer F, Schulte-Merker S (Eds.), Developmental Aspects of the Lymphatic Vascular System. Advances in Anatomy, Embryology and Cell Biology, Vol. 214. Springer, Vienna, p.119–141. Google Scholar
  34. Imai T, Hieshima K, Haskell C, et al., 1997. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell, 91(4):521–530. PubMedGoogle Scholar
  35. Jackson DG, 2014. Lymphatic regulation of cellular trafficking. J Clin Cell Immunol, 5:258. PubMedPubMedCentralGoogle Scholar
  36. Jeanbart L, Ballester M, de Titta A, et al., 2014. Enhancing efficacy of anticancer vaccines by targeted delivery to tumor-draining lymph nodes. Cancer Immunol Res, 2(5): 436–447. PubMedGoogle Scholar
  37. Jeltsch M, Kaipainen A, Joukov V, et al., 1997. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science, 276(5317):1423–1425. PubMedGoogle Scholar
  38. Jiang XG, Shapiro DJ, 2014. The immune system and inflammation in breast cancer. Mol Cell Endocrinol, 382(1): 673–682. PubMedGoogle Scholar
  39. Jiang XG, Nicolls MR, Tian W, et al., 2018. Lymphatic dysfunction, leukotrienes, and lymphedema. Ann Rev Physiol, 80:49–70. Google Scholar
  40. Kabashima K, Shiraishi N, Sugita K, et al., 2007a. CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells. Am J Pathol, 171(4):1249–1257. PubMedPubMedCentralGoogle Scholar
  41. Kabashima K, Sugita K, Shiraishi N, et al., 2007b. CXCR4 engagement promotes dendritic cell survival and maturation. Biochem Biophys Res Commun, 361(4):1012–1016. PubMedGoogle Scholar
  42. Karaman S, Detmar M, 2014. Mechanisms of lymphatic metastasis. J Clin Invest, 124(3):922–928. PubMedPubMedCentralGoogle Scholar
  43. Karlsson MC, Gonzalez SF, Welin J, et al., 2017. Epithelial-mesenchymal transition in cancer metastasis through the lymphatic system. Mol Oncol, 11(7):781–791. PubMedPubMedCentralGoogle Scholar
  44. Kerjaschki D, Bago-Horvath Z, Rudas M, et al., 2011. Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse. J Clin Invest, 121(5):2000–2012. PubMedPubMedCentralGoogle Scholar
  45. Kim S, Chung M, Jeon NL, 2016. Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro. Biomaterials, 78:115–128. PubMedGoogle Scholar
  46. Kimura T, Sugaya M, Oka T, et al., 2015. Lymphatic dysfunction attenuates tumor immunity through impaired antigen presentation. Oncotarget, 6(20):18081–18093. PubMedPubMedCentralGoogle Scholar
  47. Lambert AW, Pattabiraman DR, Weinberg RA, 2017. Emerging biological principles of metastasis. Cell, 168(4):670–691. PubMedPubMedCentralGoogle Scholar
  48. Lane RS, Femel J, Breazeale AP, et al., 2018. IFNγ-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin. J Exp Med, 215(12):3057. PubMedPubMedCentralGoogle Scholar
  49. Lee JW, Epardaud M, Sun J, et al., 2007. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol, 8(2):181–190. PubMedGoogle Scholar
  50. Lopez Gelston CA, Balasubbramanian D, Abouelkheir GR, et al., 2018. Enhancing renal lymphatic expansion prevents hypertension in mice. Circul Res, 122(8):1094–1101. Google Scholar
  51. Lukacs-Kornek V, Malhotra D, Fletcher AL, et al., 2011. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat Immunol, 12(11):1096–1104. PubMedPubMedCentralGoogle Scholar
  52. Lund AW, Duraes FV, Hirosue S, et al., 2012. VEGF-C promotes immune tolerance in B16 melanomas and crosspresentation of tumor antigen by lymph node lymphatics. Cell Rep, 1(3):191–199. PubMedGoogle Scholar
  53. Lund AW, Wagner M, Fankhauser M, et al., 2016. Lymphatic vessels regulate immune microenvironments in human and murine melanoma. J Clin Invest, 126(9):3389–3402. PubMedPubMedCentralGoogle Scholar
  54. Mäkinen T, Norrmén C, Petrova TV, 2007. Molecular mechanisms of lymphatic vascular development. Cell Mol Life Sci, 64(15):1915–1929. PubMedGoogle Scholar
  55. Malhotra D, Fletcher AL, Astarita J, et al., 2012. Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nat Immunol, 13(5):499–510. PubMedPubMedCentralGoogle Scholar
  56. Mlecnik B, Bindea G, Kirilovsky A, et al., 2016. The tumor microenvironment and immunoscore are critical determinants of dissemination to distant metastasis. Sci Transl Med, 8(327):327ra26. PubMedGoogle Scholar
  57. Mortimer PS, Rockson SG, 2014. New developments in clinical aspects of lymphatic disease. J Clin Invest, 124(3): 915–921. PubMedPubMedCentralGoogle Scholar
  58. Müller A, Homey B, Soto H, et al., 2001. Involvement of chemokine receptors in breast cancer metastasis. Nature, 410(6824):50–56. PubMedGoogle Scholar
  59. Nandi P, Girish GV, Majumder M, et al., 2017. PGE2 promotes breast cancer-associated lymphangiogenesis by activation of EP4 receptor on lymphatic endothelial cells. BMC Cancer, 17:11. PubMedPubMedCentralGoogle Scholar
  60. Nichols LA, Chen YM, Colella TA, et al., 2007. Deletional self-tolerance to a melanocyte/melanoma antigen derived from tyrosinase is mediated by a radio-resistant cell in peripheral and mesenteric lymph nodes. J Immunol, 179(2):993–1003. PubMedGoogle Scholar
  61. Nishikawa H, Sakaguchi S, 2014. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol, 27:1–7. PubMedGoogle Scholar
  62. Nörder M, Gutierrez MG, Zicari S, et al., 2012. Lymph node-derived lymphatic endothelial cells express functional costimulatory molecules and impair dendritic cell-induced allogenic T-cell proliferation. FASEB J, 26(7): 2835–2846. PubMedGoogle Scholar
  63. Paduch R, 2016. The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cell Oncol, 39(5):397–410. Google Scholar
  64. Pflicke H, Sixt M, 2009. Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. J Exp Med, 206(13):2925–2935. PubMedPubMedCentralGoogle Scholar
  65. Proulx ST, Detmar M, 2013. Molecular mechanisms and imaging of lymphatic metastasis. Exp Cell Res, 319(11): 1611–1617. PubMedGoogle Scholar
  66. Randolph GJ, Ivanov S, Zinselmeyer BH, et al., 2016. The lymphatic system: integral roles in immunity. Annu Rev Immunol, 35:31–52. PubMedPubMedCentralGoogle Scholar
  67. Robbins PD, Morelli AE, 2014. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol, 14(3): 195–208. PubMedPubMedCentralGoogle Scholar
  68. Roberts EW, Broz ML, Binnewies M, et al., 2016. Critical role for CD103+/CD141+ dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. Cancer Cell, 30(2):324–336. PubMedPubMedCentralGoogle Scholar
  69. Rockson SG, Tian W, Jiang XG, et al., 2018. Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight, 3(20):e123775. PubMedCentralGoogle Scholar
  70. Rohner NA, McClain J, Tuell SL, et al., 2015. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage. FASEB J, 29(11):4512–4522. PubMedPubMedCentralGoogle Scholar
  71. Roozendaal R, Mempel TR, Pitcher LA, et al., 2009. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity, 30(2):264–276. PubMedPubMedCentralGoogle Scholar
  72. Sainz-Jaspeado M, Claesson-Welsh L, 2018. Cytokines regulating lymphangiogenesis. Curr Opin Immunol, 53:58–63. PubMedGoogle Scholar
  73. Schoenborn JR, Wilson CB, 2007. Regulation of interferon-γ during innate and adaptive immune responses. Adv Immunol, 96:41–101. PubMedGoogle Scholar
  74. Schumacher TN, Schreiber RD, 2015. Neoantigens in cancer immunotherapy. Science, 348(6230):69–74. PubMedGoogle Scholar
  75. Shayan R, Achen MG, Stacker SA, 2006. Lymphatic vessels in cancer metastasis: bridging the gaps. Carcinogenesis, 27(9):1729–1738. PubMedGoogle Scholar
  76. Shin K, Kataru RP, Park HJ, et al., 2015. TH2 cells and their cytokines regulate formation and function of lymphatic vessels. Nat Commun, 6:6196. PubMedGoogle Scholar
  77. Skobe M, Hawighorst T, Jackson DG, et al., 2001. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med, 7(2):192–198. PubMedGoogle Scholar
  78. Stacker SA, Caesar C, Baldwin ME, et al., 2001. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med, 7(2):186–191. PubMedGoogle Scholar
  79. Stacker SA, Williams SP, Karnezis T, et al., 2014. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer, 14(3):159–172. PubMedGoogle Scholar
  80. Stump B, Cui Y, Kidambi P, et al., 2017. Lymphatic changes in respiratory diseases: more than just remodeling of the lung? Am J Respir Cell Mol Biol, 57(3):272–279. PubMedPubMedCentralGoogle Scholar
  81. Su WC, Shiesh SC, Liu HS, et al., 2001. Expression of oncogene products HER2/Neu and Ras and fibrosis-related growth factors bFGF, TGF-β, and PDGF in bile from biliary malignancies and inflammatory disorders. Dig Dis Sci, 46(7):1387–1392.PubMedGoogle Scholar
  82. Tammela T, Alitalo K, 2010. Lymphangiogenesis: molecular mechanisms and future promise. Cell, 140(4):460–476. PubMedGoogle Scholar
  83. Tewalt EF, Cohen JN, Rouhani SJ, et al., 2012. Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood, 120(24):4772–4782. PubMedPubMedCentralGoogle Scholar
  84. Thomas SN, Vokali E, Lund AW, et al., 2014. Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response. Biomaterials, 35(2):814–824. PubMedGoogle Scholar
  85. Thomas SN, Rohner NA, Edwards EE, 2016. Implications of lymphatic transport to lymph nodes in immunity and immunotherapy. Annu Rev Biomed Eng, 18:207–233. PubMedPubMedCentralGoogle Scholar
  86. Tian W, Rockson SG, Jiang XG, et al., 2017. Leukotriene B4 antagonism ameliorates experimental lymphedema. Sci Transl Med, 9(389):eaal3920. PubMedGoogle Scholar
  87. Ueba T, Nosaka T, Takahashi JA, et al., 1994. Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cells. Proc Natl Acad Sci USA, 91(19):9009–9013. PubMedGoogle Scholar
  88. Uramoto H, Hackzell A, Wetterskog D, et al., 2004. pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF β-receptor transcription. J Cell Sci, 117(17):3855–3865. PubMedGoogle Scholar
  89. Vaahtomeri K, Karaman S, Makinen T, et al., 2017. Lymphangiogenesis guidance by paracrine and pericellular factors. Genes Dev, 31(16):1615–1634. PubMedPubMedCentralGoogle Scholar
  90. Varricchi G, Loffredo S, Galdiero MR, et al., 2018. Innate effector cells in angiogenesis and lymphangiogenesis. Curr Opin Immunol, 53:152–160. PubMedGoogle Scholar
  91. Vieira JM, Norman S, del Campo CV, et al., 2018. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest, 128(8): 3402–3412. PubMedPubMedCentralGoogle Scholar
  92. Wei R, Lv MQ, Li F, et al., 2017. Human CAFs promote lymphangiogenesis in ovarian cancer via the Hh-VEGF-C signaling axis. Oncotarget, 8(40):67315–67328. PubMedPubMedCentralGoogle Scholar
  93. Weichand B, Popp R, Dziumbla S, et al., 2017. S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1β. J Exp Med, 214(9):2695–2713. PubMedPubMedCentralGoogle Scholar
  94. Wong BW, Wang XW, Zecchin A, et al., 2017. The role of fatty acid β-oxidation in lymphangiogenesis. Nature, 542(7639):49–54. PubMedGoogle Scholar
  95. Yamada A, Nagahashi M, Aoyagi T, et al., 2018. ABCC1-exported sphingosine-1-phosphate, produced by Sphingosine kinase 1, shortens survival of mice and patients with breast cancer. Mol Cancer Res, 16(6):1059–1070. PubMedPubMedCentralGoogle Scholar
  96. Yeo KP, Angeli V, 2017. Bidirectional crosstalk between lymphatic endothelial cell and T cell and its implications in tumor immunity. Front Immunol, 8:83. PubMedPubMedCentralGoogle Scholar
  97. Yu PC, Wilhelm K, Dubrac A, et al., 2017. FGF-dependent metabolic control of vascular development. Nature, 545(7653):224–228. PubMedPubMedCentralGoogle Scholar
  98. Zheng W, Tammela T, Yamamoto M, et al., 2011. Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor. Blood, 118(4):1154–1162. PubMedGoogle Scholar
  99. Zheng W, Aspelund A, Alitalo K, 2014. Lymphangiogenic factors, mechanisms, and applications. J Clin Invest, 124(3):878–887. PubMedPubMedCentralGoogle Scholar

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© Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.VA Palo Alto Health Care SystemStanford University School of MedicinePalo AltoUSA

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