Interleukins and colon cancer

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Tumor development is interpreted as a phenomenon escaping immunosurveillance.Furthermore, tumor tissue seems to have little immunogenic power.However, a variable proportion of lymphocytic infiltration may be identified in tumors, and colorectal cancer is an example of a tumor with considerable T-cell infiltration overall, which seems to be associated with a better prognosis (1,2).In fact, in both human gastric and human rectal cancers, infiltrating lymphocytes are predominantly of the Th1 and cytotoxic-1 T-cell types, with gamma-interferon predominating over other Th2-dependent cytokines including IL-4, which may be important for anti-tumoral immune response (3).For example: while studying these immunologic issues in human colorectal cancer, tumors expressed CCR5 -in association with its ligand: RANTES-and CXCR3 (Th1 markers) in marginal tumor infiltrates; CCR4 (Th2 marker) expression was rarer, which would indicate recruitment of Th1 cells and both CD8 and CD4+ cytotoxic T cells towards tumoral tissue (4).The role of specific cytokines -including chemokines-in immune defense against tumor development and extension is being currently assessed by multiple studies oriented towards the design of effective immunobiologic anti-tumoral therapies.Most of them are experimental, albeit a number of therapeutic attempts in humans already exist in view of the not-so-good prospects of surgery, radiotherapy, and chemotherapy for advanced-stage tumors.However, specific cytokines may on occasion encourage tumor growth and particularly tumor spread, as is the case with IL-1β and TNFα, which are released for instance during surgery and may activate adhesion molecules (ICAM-1 and VCAM-1, and their ligands LFA-1 and VLA-4) at the lung's vascular endothelium, thus promoting pulmonary metastasis (5).In a study carried out in patients with colon carcinoma serum IL-6, TNFα and PCR levels were seen to correlate with prognosis in terms of tumor mass and survival (6), while IL-6 and TGFα levels, and to a lesser extent TNFα levels, were seen to correlate with quality of life (7).Regarding the liver, experimental studies have suggested that Kupffer cells may well release IL-6, IL-10 and TNFα when stimulated by carcinoembrionary antigen (CEA).This may induce ICAM-1 expression and a greater potential for neoplastic cell retention within sinusoids, thus resulting in colon carcinoma metastases to the liver (8).Regarding cytokines, IL-2 and IL-12 are most involved in immunobiological anti-tumoral response (9).As for IL-2, its local administration in transplanted colon carcinoma induced a macrophage response with tumor necrosis, while systemic administration had no effect other than notable adverse events (10).Other authors identified a rejection of specific colon tumors in mice following vaccination using dendritic cells loaded with anti-idiotype 3H1 antibodies (which mimics carcinoem- Interleukins and colon cancer

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