Presence of the T-cell activation marker OX-40 on tumor infiltrating lymphocytes and draining lymph node cells from patients with melanoma and head and neck cancers

doi:10.1016/S0002-9610(97)00139-6

The American Journal of Surgery

Volume 174, Issue 3, September 1997, Pages 258-265

https://doi.org/10.1016/S0002-9610(97)00139-6 Get rights and content

Abstract

Background

The OX-40 antigen is a cell surface glycoprotein in the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells. Selective target organ expression of the OX-40 receptor on autoantigen specific T cells has been found in autoimmune disease. In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assessed in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients with head and neck squamous cell carcinomas and 9 patients with melanomas.

Methods

Cell phenotype was determined by fluorescence cell analysis using a monoclonal antibody to human OX-40, and CD4+ T cell lymphokine production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR).

Results

Expression of the OX-40 receptor was found in as many as 31% of the TILs and as many as 28% of the DLNCs tested. Conversely, no OX-40 expression was found in PBLs. In addition, CD4+ T cells isolated from DLNCs (but not from TILs or PBLs) secreted a Th1 pattern of cytokines (IL-2, gamma Interferon). Co-culture of autologous CD4+ TILs with an MHC class II+ melanoma cell line transfected with OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumor regression.

Conclusions

These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumorspecific population of activated T cells capable of mediating tumor reactivity. These cells may play an exploitable role in future trials of immunotherapy.

References (36)

HintzenRQ et al.
CD27: a marker and mediator of T-cell activation?
Immunology Today
(1994)
CallardR et al.
CD40 ligand and its role in X-linked hyper-IgM syndrome
Immunology Today
(1993)
PatersonDJ et al.
Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts
Molecular Immunol
(1987)
StuberE et al.
Crosslinking of OX-40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic
B cells. Immunity
(1995)
LenschowDJ et al.
CD28/B7 system of T cell co-stimulation
Ann Rev Immunol
(1996)
RosensteinM et al.
Adoptive immunotherapy of established syngeneic solid tumors: role of T-lymphoid cell populations
J Immunol
(1984)
BazzoniF et al.
The tumor necrosis factor ligand and receptor families
NEJM
(1996)
GodfreyWR et al.
Identification of a human Ox40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor
J Exp Med
(1994)
WeinbergAD et al.
The OX-40 antibody selects for autoantigen specific V beta 8.2 + T cells within the spinal cord of Lewis rats with autoimmune encephalomyelitis
J Neurosci Res
(1996)
WeinbergAD et al.
Target organ specific up regulation of the MRC OX-40 marker and selective production of Th1 lymphokine mRNA by encephalitogenic T helper cells isolated from the spinal cord of rats with experimental autoimmune encephalomyelitis
J Immunol
(1994)

MiltenyiS et al.

High gradient magnetic cell separation with MACS

Cytometry

(1990)

ChomeczynskiP et al.

Single step method of RNA isolation by acid guanidinium thiocyanated-pheno-chloroform extraction

Ann Biochem

(1987)

ChowYK et al.

Immunity to TCR peptides in multiple sclerosis: T cell recognition of V beta 5.2. V beta 6.1. CDR2 peptides

J Immunol

(1994)

MiyawakiT et al.

Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood

J Immunol

(1992)

Watanabe-FukunagaR et al.

Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis

Nature

(1992)

GodfreyWR et al.

Identification of a human OX-40 ligand, a co-stimulator of CD4+ T cells with homology to tumor necrosis factor

J Exp Med

(1994)

BaumPR et al.

Molecular characterization of immune and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34

EMBO

(1994)

MallettS et al.

Characterization of the MRC OX-40 antigen of activated CD4 positive T lymphocytes—a molecule related to nerve growth factor receptor

EMBO

(1990)

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^*: Presented at the 87th Annual Meeting of the American Association for Cancer Research, Washington, DC, April 20–24, 1996.

View full text

Presence of the T-cell activation marker OX-40 on tumor infiltrating lymphocytes and draining lymph node cells from patients with melanoma and head and neck cancers*

Abstract

Background

Methods

Results

Conclusions

Immunology Today

Immunology Today

Molecular Immunol

B cells. Immunity

CD28/B7 system of T cell co-stimulation

Ann Rev Immunol

Adoptive immunotherapy of established syngeneic solid tumors: role of T-lymphoid cell populations

J Immunol

The tumor necrosis factor ligand and receptor families

NEJM

Identification of a human Ox40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor

J Exp Med

The OX-40 antibody selects for autoantigen specific V beta 8.2 + T cells within the spinal cord of Lewis rats with autoimmune encephalomyelitis

J Neurosci Res

Target organ specific up regulation of the MRC OX-40 marker and selective production of Th1 lymphokine mRNA by encephalitogenic T helper cells isolated from the spinal cord of rats with experimental autoimmune encephalomyelitis

J Immunol

High gradient magnetic cell separation with MACS

Cytometry

Single step method of RNA isolation by acid guanidinium thiocyanated-pheno-chloroform extraction

Ann Biochem

Immunity to TCR peptides in multiple sclerosis: T cell recognition of V beta 5.2. V beta 6.1. CDR2 peptides

J Immunol

Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood

J Immunol

Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis

Nature

Identification of a human OX-40 ligand, a co-stimulator of CD4+ T cells with homology to tumor necrosis factor

J Exp Med

Molecular characterization of immune and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34

EMBO

Characterization of the MRC OX-40 antigen of activated CD4 positive T lymphocytes—a molecule related to nerve growth factor receptor

EMBO