MHC Class II Antigen Presentation by Lymphatic Endothelial Cells in Tumors Promotes Intratumoral Regulatory T cell-Suppressive Functions.
Animals
Antigen Presentation
Cell Communication
/ immunology
Coculture Techniques
Disease Models, Animal
Endothelial Cells
/ immunology
Female
Histocompatibility Antigens Class II
/ metabolism
Humans
Lymph Nodes
/ cytology
Lymphatic Vessels
/ cytology
Mice
Neoplasms
/ immunology
Primary Cell Culture
T-Lymphocytes, Regulatory
/ immunology
Tumor Cells, Cultured
Tumor Escape
Tumor Microenvironment
/ immunology
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
16
09
2020
revised:
09
03
2021
accepted:
04
05
2021
pubmed:
7
5
2021
medline:
22
2
2022
entrez:
6
5
2021
Statut:
ppublish
Résumé
Several solid malignancies trigger lymphangiogenesis, facilitating metastasis. Tumor-associated lymphatic vessels significantly contribute to the generation of an immunosuppressive tumor microenvironment (TME). Here, we have investigated the ability of tumoral lymphatic endothelial cells (LEC) to function as MHC class II-restricted antigen-presenting cells in the regulation of antitumor immunity. Using murine models of lymphangiogenic tumors engrafted under the skin, we have shown that tumoral LECs upregulate MHC class II and the MHC class II antigen-processing machinery, and that they promote regulatory T-cell (Treg) expansion
Identifiants
pubmed: 33952631
pii: 2326-6066.CIR-20-0784
doi: 10.1158/2326-6066.CIR-20-0784
doi:
Substances chimiques
Histocompatibility Antigens Class II
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
748-764Subventions
Organisme : NCI NIH HHS
ID : R01 CA219304
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
Références
Motz GT, Coukos G. Deciphering and reversing tumor immune suppression. Immunity. 2013;39:61–73.
Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 2006;6:715–27.
Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.
Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306.
Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010;127:759–67.
De Simone M, Arrigoni A, Rossetti G, Gruarin P, Ranzani V, Politano C, et al. Transcriptional landscape of human tissue lymphocytes unveils uniqueness of tumor-infiltrating T regulatory cells. Immunity. 2016;45:1135–47.
Plitas G, Konopacki C, Wu K, Bos PD, Morrow M, Putintseva EV, et al. Regulatory T cells exhibit distinct features in human breast cancer. Immunity. 2016;45:1122–34.
Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer. 2014;14:159–72.
Olszewski WL. The innate reaction of the human skin lymphatic system to foreign and self-antigens. Lymphat Res Biol. 2005;3:50–57.
Pugh CW, MacPherson GG, Steer HW. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med. 1983;157:1758–79.
Mackay CR, Marston WL, Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990;171:801–17.
Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol. 2005;5:617–28.
Malhotra D, Fletcher AL, Astarita J, Lukacs-Kornek V, Tayalia P, Gonzalez SF, et al. Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nat Immunol. 2012;13:499–510.
Berendam SJ, Koeppel AF, Godfrey NR, Rouhani SJ, Woods AN, Rodriguez AB, et al. Comparative transcriptomic analysis identifies a range of immunologically related functional elaborations of lymph node associated lymphatic and blood endothelial cells. Front Immunol. 2019;10:816.
Grigorova IL, Schwab SR, Phan TG, Pham TH, Okada T, Cyster JG. Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat Immunol. 2009;10:58–65.
Pham TH, Baluk P, Xu Y, Grigorova I, Bankovich AJ, Pappu R, et al. Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning. J Exp Med. 2010;207:17–27.
Mendoza A, Fang V, Chen C, Serasinghe M, Verma A, Muller J, et al. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells. Nature. 2017;546:158–61.
Lukacs-Kornek V, Malhotra D, Fletcher AL, Acton SE, Elpek KG, Tayalia P, et al. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat Immunol. 2011;12:1096–104.
Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph GJ, et al. Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J Immunol. 2009;183:1767–79.
Christiansen AJ, Dieterich LC, Ohs I, Bachmann SB, Bianchi R, Proulx ST, et al. Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation. Oncotarget. 2016;7:39421–35.
Cohen JN, Guidi CJ, Tewalt EF, Qiao H, Rouhani SJ, Ruddell A, et al. Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation. J Exp Med. 2010;207:681–8.
Fletcher AL, Lukacs-Kornek V, Reynoso ED, Pinner SE, Bellemare-Pelletier A, Curry MS, et al. Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J Exp Med. 2010;207:689–97.
Tewalt EF, Cohen JN, Rouhani SJ, Guidi CJ, Qiao H, Fahl SP, et al. Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood. 2012;120:4772–82.
Hirosue S, Vokali E, Raghavan VR, Rincon-Restrepo M, Lund AW, Corthesy-Henrioud P, et al. Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: a new role for lymphatic endothelial cells. J Immunol. 2014;192:5002–11.
Rouhani SJ, Eccles JD, Riccardi P, Peske JD, Tewalt EF, Cohen JN, et al. Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction. Nat Commun. 2015;6:6771.
Dubrot J, Duraes FV, Potin L, Capotosti F, Brighouse D, Suter T, et al. Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4(+) T cell tolerance. J Exp Med. 2014;211:1153–66.
Dubrot J, Duraes FV, Harle G, Schlaeppi A, Brighouse D, Madelon N, et al. Absence of MHC-II expression by lymph node stromal cells results in autoimmunity. Life Sci Alliance. 2018;1:e201800164.
Nadafi R, Gago de Graca C, Keuning ED, Koning JJ, de Kivit S, Konijn T, et al. Lymph node stromal cells generate antigen-specific regulatory T cells and control autoreactive T and B cell responses. Cell Rep. 2020;30:4110–23.
Swartz MA, Lund AW. Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nat Rev Cancer. 2012;12:210–9.
Lund AW, Duraes FV, Hirosue S, Raghavan VR, Nembrini C, Thomas SN, et al. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 2012;1:191–9.
Dieterich LC, Ikenberg K, Cetintas T, Kapaklikaya K, Hutmacher C, Detmar M. Tumor-associated lymphatic vessels upregulate PDL1 to inhibit T-cell activation. Front Immunol. 2017;8:66.
Lane RS, Femel J, Breazeale AP, Loo CP, Thibault G, Kaempf A, et al. IFNgamma-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin. J Exp Med. 2018;215:3057–74.
Fankhauser M, Broggi MAS, Potin L, Bordry N, Jeanbart L, Lund AW, et al. Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma. Sci Transl Med. 2017;9:eaal4712.
Barnden MJ, Allison J, Heath WR, Carbone FR. Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements. Immunol Cell Biol. 1998;76:34–40.
Bazigou E, Lyons OT, Smith A, Venn GE, Cope C, Brown NA, et al. Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice. J Clin Invest. 2011;121:2984–92.
Lee HM, Fleige A, Forman R, Cho S, Khan AA, Lin LL, et al. IFNgamma signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells. PLoS Pathog. 2015;11:e1004635.
Yang BH, Hagemann S, Mamareli P, Lauer U, Hoffmann U, Beckstette M, et al. Foxp3(+) T cells expressing RORgammat represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol. 2016;9:444–57.
Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J, Eberl G, et al. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med. 2007;204:57–63.
Guery L, Dubrot J, Lippens C, Brighouse D, Malinge P, Irla M, et al. Ag-presenting CpG-activated pDCs prime Th17 cells that induce tumor regression. Cancer Res. 2014;74:6430–40.
Choi I, Lee S, Hong YK. The new era of the lymphatic system: no longer secondary to the blood vascular system. Cold Spring Harb Perspect Med. 2012;2:a006445.
DuPage M, Dooley AL, Jacks T. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat Protoc. 2009;4:1064–72.
Preibisch S, Saalfeld S, Tomancak P. Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics. 2009;25:1463–5.
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3:RESEARCH0034.
Reith W, LeibundGut-Landmann S, Waldburger JM. Regulation of MHC class II gene expression by the class II transactivator. Nat Rev Immunol. 2005;5:793–806.
Tamburini BA, Burchill MA, Kedl RM. Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection. Nat Commun. 2014;5:3989.
Miragaia RJ, Gomes T, Chomka A, Jardine L, Riedel A, Hegazy AN, et al. Single-cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation. Immunity. 2019;50:493–504.
Tammela T, Alitalo K. Lymphangiogenesis: molecular mechanisms and future promise. Cell. 2010;140:460–76.
Ma Q, Dieterich LC, Detmar M. Multiple roles of lymphatic vessels in tumor progression. Curr Opin Immunol. 2018;53:7–12.
Ma Q, Dieterich LC, Ikenberg K, Bachmann SB, Mangana J, Proulx ST, et al. Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread. Sci Adv. 2018;4:eaat4758.
Lund AW, Wagner M, Fankhauser M, Steinskog ES, Broggi MA, Spranger S, et al. Lymphatic vessels regulate immune microenvironments in human and murine melanoma. J Clin Invest. 2016;126:3389–402.
Sasso MS, Mitrousis N, Wang Y, Briquez PS, Hauert S, Ishihara J, et al. Lymphangiogenesis-inducing vaccines elicit potent and long-lasting T cell immunity against melanomas. Sci Adv. 2021;7:eabe4362.
Cohen JN, Tewalt EF, Rouhani SJ, Buonomo EL, Bruce AN, Xu X, et al. Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment. PLoS One. 2014;9:e87740.
Magnuson AM, Kiner E, Ergun A, Park JS, Asinovski N, Ortiz-Lopez A, et al. Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types. Proc Natl Acad Sci U S A. 2018;115:E10672–E10681.
Chaudhry A, Rudensky AY. Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest. 2013;123:939–44.
Cretney E, Kallies A, Nutt SL. Differentiation and function of Foxp3(+) effector regulatory T cells. Trends Immunol. 2013;34:74–80.
Franchini DM, Lanvin O, Tosolini M, Patras de Campaigno E, Cammas A, Pericart S, et al. Microtubule-driven stress granule dynamics regulate inhibitory immune checkpoint expression in T cells. Cell Rep. 2019;26:94–107.
Peske JD, Thompson ED, Gemta L, Baylis RA, Fu YX, Engelhard VH. Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity. Nat Commun. 2015;6:7114.
Thompson ED, Enriquez HL, Fu YX, Engelhard VH. Tumor masses support naive T cell infiltration, activation, and differentiation into effectors. J Exp Med. 2010;207:1791–804.
Piao W, Xiong Y, Li L, Saxena V, Smith KD, Hippen KL, et al. Regulatory T cells condition lymphatic endothelia for enhanced transendothelial migration. Cell Rep. 2020;30:1052–62.
Richards H, Williams A, Jones E, Hindley J, Godkin A, Simon AK, et al. Novel role of regulatory T cells in limiting early neutrophil responses in skin. Immunology. 2010;131:583–92.