The effect of colorectal cancer upon host peripheral immune cell function.
OBJECTIVE
Colorectal cancer is immunogenic. However, it is also associated with suppression of host immunity. Identifying the mechanisms involved in immune suppression is necessary to develop future immunotherapeutic strategies. The aim of this study was to assess immune cell function in colorectal cancer patients.


METHODS
A total of 80 colorectal cancer patients (41 male) prior to treatment and 38 matched controls (21 male) were recruited. Venous blood samples were taken. White blood cell composition was determined using monoclonal antibodies. Levels of cytokines IFN-gamma, TNF-alpha, IL-2, IL-10, IL-4 and IL-6 were measured from the supernatants of activated peripheral blood mononuclear cells (PBMC) following thawing and re-suspension. Peripheral blood mononuclear proliferation was measured using 3H-Thymidine.


RESULTS
Stage I-III cancer patients had elevated percentages of CD8 T cell (P = 0.004) whilst stage IV patients had low total lymphocyte percentages (P = 0.016). Monocyte and NKT cell percentage decreased with advanced tumour stages (P = 0.013 and P = 0.038). Patients had lower PBMC proliferation and production of the TH1 cytokines (IFN-gamma and TNF-alpha) (P < 0.001) than that of the controls. IL-6 and IL-4 production were not significantly different. IFN-gamma and TNF-alpha concentrations reduced with tumour vascular invasion (P = 0.011 and P = 0.019).


CONCLUSIONS
Colorectal cancer induces an immunological response, shifting the cytokine balance. The most profound changes are seen once disease has spread systemically.
Evans
C F M
CF
St Georges University of London, Cranmer Terrace, London, UK.
Galustian
C
C
Bodman-Smith
M
M
Dalgleish
A G
AG
Kumar
D
D
D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D016130:Immunophenotyping; D007371:Interferon-gamma; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma