Cancer Immunology, Immunotherapy

, Volume 56, Issue 3, pp 359–370

Colon carcinoma cells induce CXCL11-dependent migration of CXCR3-expressing cytotoxic T lymphocytes in organotypic culture

  • Klara Berencsi
  • Neal J. Meropol
  • John P. Hoffman
  • Elin Sigurdson
  • Lydia Giles
  • Pyapalli Rani
  • Rajasekharan Somasundaram
  • Tianqian Zhang
  • Jiri Kalabis
  • Laura Caputo
  • Emma Furth
  • Rolf Swoboda
  • Francesco Marincola
  • Dorothee Herlyn
Original Article

DOI: 10.1007/s00262-006-0190-2

Cite this article as:
Berencsi, K., Meropol, N.J., Hoffman, J.P. et al. Cancer Immunol Immunother (2007) 56: 359. doi:10.1007/s00262-006-0190-2

Abstract

Adoptive immunotherapy of cancer patients with cytolytic T lymphocytes (CTL) has been hampered by the inability of the CTL to home into tumors in vivo. Chemokines can attract T lymphocytes to the tumor site, as demonstrated in animal models, but the role of chemokines in T-lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the role of chemokines and their receptors in the migration of a colon carcinoma (CC) patient’s CTL toward autologous tumor cells has been studied in a novel three-dimensional organotypic CC culture. CTL migration was mediated by chemokine receptor CXCR3 expressed by the CTL and CXCL11 chemokine secreted by the tumor cells. Excess CXCL11 or antibodies to CXCL11 or CXCR3 inhibited migration of CTL to tumor cells. T cell and tumor cell analyses for CXCR3 and CXCL11 expression, respectively, in ten additional CC samples, may suggest their involvement in other CC patients. Our studies, together with previous studies indicating angiostatic activity of CXCL11, suggest that CXCL11 may be useful as an immunotherapeutic agent for cancer patients when transduced into tumor cells or fused to tumor antigen-specific Ab.

Keywords

CTL Chemokines Chemotaxis Apoptosis Tumor immunity 

Abbreviations

Ab

Antibody

Ag

Antigen

CC

Colon carcinoma

CTL

Cytotoxic T lymphocyte

DC

Dendritic cell

EBV

Epstein–Barr virus

E:T

Effector-to-target ratio

FCFB/1

Fetal colon fibroblast

GM-CSF

Granulocyte–macrophage colony-stimulating factor

IFN

Interferon

IL

Interleukin

LAK

Lymphokine-activated killer

mAb

Monoclonal antibody

MLTC

Mixed lymphocyte tumor cell culture

PBMC

Peripheral blood mononuclear cells

PCR

Polymerase chain reaction

TIL

Tumor infiltrating lymphocytes

TNF

Tumor necrosis factor

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Klara Berencsi
    • 1
  • Neal J. Meropol
    • 2
    • 3
  • John P. Hoffman
    • 2
  • Elin Sigurdson
    • 2
  • Lydia Giles
    • 2
  • Pyapalli Rani
    • 1
  • Rajasekharan Somasundaram
    • 1
  • Tianqian Zhang
    • 1
  • Jiri Kalabis
    • 1
  • Laura Caputo
    • 1
  • Emma Furth
    • 4
  • Rolf Swoboda
    • 1
  • Francesco Marincola
    • 5
  • Dorothee Herlyn
    • 1
  1. 1.The Wistar InstitutePhiladelphiaUSA
  2. 2.Division of Medical ScienceFox Chase Cancer CenterPhiladelphiaUSA
  3. 3.Division of Population ScienceFox Chase Cancer CenterPhiladelphiaUSA
  4. 4.Department of Pathology and Laboratory MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA
  5. 5.Immunogenetics Section, Department of Transfusion Medicine, Clinical Center National Institutes of HealthBethesdaUSA

Personalised recommendations