Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa.
Worldwide, gastric adenocarcinoma (GC) is the second most common cause of death from malignant disease. The reason why immune responses are unable to clear the tumour is not fully understood, although aberrant lymphocyte recruitment to the tumour site might be one factor. Therefore, we investigated the homing phenotype of mucosal T lymphocytes in GC, compared to tumour-free mucosa. We could detect significantly decreased frequencies of mucosal homing alpha4beta7+ T cells in the tumour tissues and increased frequencies of L-selectin+ T cells. This was probably due to the correlated decrease in MAdCAM-1 positive and increase in PNAd positive blood vessels in the tumour mucosa. There were also fewer CXCR3+ T lymphocytes in the tumour tissue. These findings provide evidence that endothelial cells within tumours arising at mucosal sites do not support extravasation of typical mucosa-infiltrating T cells. This may be of major relevance for future immunotherapeutic strategies for treatment of GC.
Enarsson
K
K
Dept. Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, and Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden. karin.enarsson@microbio.gu.se
Johnsson
E
E
Lindholm
C
C
Lundgren
A
A
Pan-Hammarström
Q
Q
Strömberg
E
E
Bergin
P
P
Baunge
E-L
EL
Svennerholm
A-M
AM
Quiding-Järbrink
M
M
D000230:Adenocarcinoma / Q000276:immunology*; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009088:Mucoproteins / Q000378:metabolism; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface; C515187:CXCR3 protein, human; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; C484074:LPL binding proteins, human; C504265:MADCAM1 protein, human; D008565:Membrane Proteins; D009088:Mucoproteins; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing