Expression and function of T cell homing molecules in Hodkins's lymphoma

Lee Machado, Ruth Jarrett, Susan Morgan, Paul Murray, Beatrix Hunter, Emma Hamilton, John Crocker, Wendy Thomas, Neil Steven, Tariq Ismail, Ann Chapman, David H Adams, S P Lee

Research output: Contribution to Book/Report typesChapterResearchpeer-review

Abstract

Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin’s lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-inWltrating T cells in HL and compared them with T cells from unaVected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to puriWed chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaVected lymph nodes. Thus, T cell recruitment to HL resembles entry of naïve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression
Original languageEnglish
Title of host publicationCancer Immunology, Immunotherapy
Pages85–94
Number of pages9
Volume58
Edition1
DOIs
Publication statusPublished - 1 Jan 2009

Publication series

NameCancer Immunology, Immunotherapy
ISSN (Print)0340-7004

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Lymphoma
T-Lymphocytes
Hodgkin Disease
Chemokine Receptors
Lymph Nodes
Ligands
Colorectal Neoplasms
Phenotype
Vascular Endothelium
Chemotaxis
Cell- and Tissue-Based Therapy
Chemokines
Neoplasms

Keywords

  • Chemokines
  • Hodgkin’s lymphoma
  • T cell homing
  • tumour immunity

Cite this

Machado, L., Jarrett, R., Morgan, S., Murray, P., Hunter, B., Hamilton, E., ... Lee, S. P. (2009). Expression and function of T cell homing molecules in Hodkins's lymphoma. In Cancer Immunology, Immunotherapy (1 ed., Vol. 58, pp. 85–94). (Cancer Immunology, Immunotherapy). https://doi.org/10.1007/s00262-008-0528-z, https://doi.org/10.1007/s00262-008-0528-z
Machado, Lee ; Jarrett, Ruth ; Morgan, Susan ; Murray, Paul ; Hunter, Beatrix ; Hamilton, Emma ; Crocker, John ; Thomas, Wendy ; Steven, Neil ; Ismail, Tariq ; Chapman, Ann ; Adams, David H ; Lee, S P. / Expression and function of T cell homing molecules in Hodkins's lymphoma. Cancer Immunology, Immunotherapy. Vol. 58 1. ed. 2009. pp. 85–94 (Cancer Immunology, Immunotherapy).
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Machado, L, Jarrett, R, Morgan, S, Murray, P, Hunter, B, Hamilton, E, Crocker, J, Thomas, W, Steven, N, Ismail, T, Chapman, A, Adams, DH & Lee, SP 2009, Expression and function of T cell homing molecules in Hodkins's lymphoma. in Cancer Immunology, Immunotherapy. 1 edn, vol. 58, Cancer Immunology, Immunotherapy, pp. 85–94. https://doi.org/10.1007/s00262-008-0528-z, https://doi.org/10.1007/s00262-008-0528-z

Expression and function of T cell homing molecules in Hodkins's lymphoma. / Machado, Lee; Jarrett, Ruth; Morgan, Susan; Murray, Paul; Hunter, Beatrix; Hamilton, Emma; Crocker, John; Thomas, Wendy; Steven, Neil; Ismail, Tariq; Chapman, Ann; Adams, David H; Lee, S P.

Cancer Immunology, Immunotherapy. Vol. 58 1. ed. 2009. p. 85–94 (Cancer Immunology, Immunotherapy).

Research output: Contribution to Book/Report typesChapterResearchpeer-review

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AU - Machado, Lee

AU - Jarrett, Ruth

AU - Morgan, Susan

AU - Murray, Paul

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AU - Hamilton, Emma

AU - Crocker, John

AU - Thomas, Wendy

AU - Steven, Neil

AU - Ismail, Tariq

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N2 - Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin’s lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-inWltrating T cells in HL and compared them with T cells from unaVected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to puriWed chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaVected lymph nodes. Thus, T cell recruitment to HL resembles entry of naïve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression

AB - Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin’s lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-inWltrating T cells in HL and compared them with T cells from unaVected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to puriWed chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaVected lymph nodes. Thus, T cell recruitment to HL resembles entry of naïve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression

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SN - 0026200805

VL - 58

T3 - Cancer Immunology, Immunotherapy

SP - 85

EP - 94

BT - Cancer Immunology, Immunotherapy

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Machado L, Jarrett R, Morgan S, Murray P, Hunter B, Hamilton E et al. Expression and function of T cell homing molecules in Hodkins's lymphoma. In Cancer Immunology, Immunotherapy. 1 ed. Vol. 58. 2009. p. 85–94. (Cancer Immunology, Immunotherapy). https://doi.org/10.1007/s00262-008-0528-z, https://doi.org/10.1007/s00262-008-0528-z