Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells

Paolo Ghia, Pietro Transidico, J. Pedro Veiga, Christoph Schaniel, Federica Sallusto, Kouji Matsushima, Stephen E. Sallan, Antonius G. Rolink, Alberto Mantovani, Lee M. Nadler, Angelo A. Cardoso

Research output: Contribution to journalArticle

Abstract

The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 crosslinking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4+ antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalBlood
Volume98
Issue number3
DOIs
Publication statusPublished - Aug 1 2001

Fingerprint

T-Cell Leukemia
B-Lymphoid Precursor Cells
T-cells
Chemotactic Factors
Ligation
Tumors
Cells
Neoplasms
T-Lymphocytes
CC Chemokines
Transendothelial and Transepithelial Migration
Neoplasm Antigens
Cancer Vaccines
Crosslinking
Cytotoxic T-Lymphocytes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunotherapy
Vaccines
Cultured Cells
Immunity

ASJC Scopus subject areas

  • Hematology

Cite this

Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells. / Ghia, Paolo; Transidico, Pietro; Pedro Veiga, J.; Schaniel, Christoph; Sallusto, Federica; Matsushima, Kouji; Sallan, Stephen E.; Rolink, Antonius G.; Mantovani, Alberto; Nadler, Lee M.; Cardoso, Angelo A.

In: Blood, Vol. 98, No. 3, 01.08.2001, p. 533-540.

Research output: Contribution to journalArticle

Ghia, P, Transidico, P, Pedro Veiga, J, Schaniel, C, Sallusto, F, Matsushima, K, Sallan, SE, Rolink, AG, Mantovani, A, Nadler, LM & Cardoso, AA 2001, 'Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells', Blood, vol. 98, no. 3, pp. 533-540. https://doi.org/10.1182/blood.V98.3.533
Ghia, Paolo ; Transidico, Pietro ; Pedro Veiga, J. ; Schaniel, Christoph ; Sallusto, Federica ; Matsushima, Kouji ; Sallan, Stephen E. ; Rolink, Antonius G. ; Mantovani, Alberto ; Nadler, Lee M. ; Cardoso, Angelo A. / Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells. In: Blood. 2001 ; Vol. 98, No. 3. pp. 533-540.
@article{e829578e9dc64425afb1669e8b5dbbf9,
title = "Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells",
abstract = "The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 crosslinking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4+ antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells.",
author = "Paolo Ghia and Pietro Transidico and {Pedro Veiga}, J. and Christoph Schaniel and Federica Sallusto and Kouji Matsushima and Sallan, {Stephen E.} and Rolink, {Antonius G.} and Alberto Mantovani and Nadler, {Lee M.} and Cardoso, {Angelo A.}",
year = "2001",
month = "8",
day = "1",
doi = "10.1182/blood.V98.3.533",
language = "English",
volume = "98",
pages = "533--540",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells

AU - Ghia, Paolo

AU - Transidico, Pietro

AU - Pedro Veiga, J.

AU - Schaniel, Christoph

AU - Sallusto, Federica

AU - Matsushima, Kouji

AU - Sallan, Stephen E.

AU - Rolink, Antonius G.

AU - Mantovani, Alberto

AU - Nadler, Lee M.

AU - Cardoso, Angelo A.

PY - 2001/8/1

Y1 - 2001/8/1

N2 - The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 crosslinking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4+ antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells.

AB - The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 crosslinking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4+ antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells.

UR - http://www.scopus.com/inward/record.url?scp=0035437192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035437192&partnerID=8YFLogxK

U2 - 10.1182/blood.V98.3.533

DO - 10.1182/blood.V98.3.533

M3 - Article

C2 - 11468146

AN - SCOPUS:0035437192

VL - 98

SP - 533

EP - 540

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -