Significance of pre-treatment immunological parameters in colorectal cancer patients with unresectable metastases to the liver

BACKGROUND/AIMS: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL) subsets and serum cytokine levels of healthy indivi duals with those of patients with unresectable liver metastases from colore ctal carcinoma before starting regional chemoimmunotherapy. Since the thera peutic responses are limited only to a subset of patients, we hypothesize t hat the initial status of immunity and individual immune response to a tumo r might be significant to the therapeutic outcome. METHODOLOGY: Cellular and humoral immunological parameters were compared be tween 10 patients with colorectal cancer metastases to the liver responding and non-responding to regional intraarterial chemo-immunotherapy, and 5 he alty individuals. Analyses included a flow cyotmetric immunophenotyping of peripheral blood mononuclear cells (CD3, CD4, CD8, CD19, CD25, CD28, CD56, CD57, CD80 and HLA.DR), estimation of serum cytokine levels of interleukin- 2 (IL-2), interleukin-4 (IL-4), interleukin-g (IL-6), tumor necrosis faccto r alpha (TNF-alpha), and other immunological parameters are soluble IL-2 re ceptor (sIL-2), carcinoembryonic antigen (CEA), gastrointestinal cancer-ass ociated antigen (CA 19-9), and C-reactive acute phase protein (CRP). A sign ificantly lower proportion of CD8 lymphocytes and a trend for decreased CD1 9, CD28 and CD80 was detected among colorectal cancer patients before liver -directed chemotherapy compared to healty controls. RESULTS: The cancer patients showed a significantly increased population of peripheral NK cells as detected by both CD56+ and CD57+ phenotypes. Elevat ed serum levels of CRP, IL-4 and TNF-alpha, sIL-2R, but not IL-2, were also demonstrated in cancer patients as compared to controls. Activated CD25+ l ymphocytes correlated negatively with CD28+ lymphocytes (r=-0.68, p<0.01) a nd less significantly with CD4+ lymphocytes (r=-0.56, p<0.05). The CD8+ cyt otoxic eel subset might be negatively influenced by serum IL-4 (r=-0.57, p< 0.05). Positive correlation was found between sIL-2R and CRP (r=-0.78, p<0. 01), and between sIL-2R and TNF-alpha (r=0.64, p<0.05) serum levels in pati ents with progressive disease during the course of therapy, the initial pro portions of CD4+, CD19+ and CD28+ lymphocytes were significantly lower than those among responders. Among humoral parameters, only sIL-2R showed a mar ginal correlation with therapeutic response, being more elevated among non- responding patients. Pre-treatment serum levels of CEA and CA 19-9 showed c orrelation with neither therapeutic response nor with any of the cellular o r humoral immunological parameters analyzed. CONCLUSIONS: The results may serve as an initial guideline to open a discus sion on the rationale of such a panel of tests, hopefully leading to standa rized laboratory pre-selection and monitoring of patients treated with regi onal chemoimmunotherapy.