The impact of preoperative immunonutrition and other nutrition models on tumor infiltrative lymphocytes in colorectal cancer patients
ABSTRACT The importance of the alteration of tumor infiltrative lymphocytes (CD4(+), CD8(+), CD16(+), and CD56(+)) in colorectal cancer prognosis is well known. In this study, we analyzed the effect of preoperative immunonutrition and different nutritional models on the clinical condition of colorectal cancer patients.
Twenty-eight colorectal cancer patients were grouped into 4 groups according to their nutrition regimens randomly and were given immunonutrition (IMN), standard enteral (SE), total parental nutrition (TPN), and normal nutrition (NN) regimens, all of which contained the same calorie-nitrogen content within a 7-day preoperative period. All patients had an endoscopic biopsy before and after the regimen, and the lymphocyte population infiltrating mucosal parts of the resected tumor tissue were evaluated. Immunohistochemical analysis of the tissue specimens was performed by staining with antihuman CD4(+), CD8(+), CD16(+), and CD56(+) antibodies.
After nutrition, there were significant increases in each of the 4 groups of CD4(+) and CD8(+) cells within the tumor. Comparing the rates of augmentation, the increased rates of the CD8(+) cells infiltrating the tumor after nutrition in the patients who were fed with IMN were significantly more than the ones in other groups (P = .01). CD16(+) cell infiltration was significantly higher in all groups except the SE and IMN groups. The SE group had increased CD56(+) cell infiltration compared with the other groups.
In the colorectal cancer patients who had nutrition in the 7-day preoperative period, except for the SE nutrition group, there were significant increases of infiltration of CD56(+) cells at the mucosal part of the tumor tissue within the CD4(+) and CD8(+) cell population. When postnutrition values were compared, there was a marked increase of CD8(+) cells in the IMN group.
[Show abstract] [Hide abstract]
ABSTRACT: The predictive value of lymphocyte infiltrates (LI) was studied in 489 patients with breast cancer followed-up for over 10 years. LI were positively correlated to axillary lymph-node status, tumour diameter and histological and morphometric variables (P less than 0.001). In a multivariate analysis LI were independently related to axillary lymph-node status. LI predicted recurrence-free survival (RFS) in rapidly proliferating tumours (P = 0.0269). LI predicted RFS (P = 0.08) and breast cancer related survival (BS) (P = 0.0164) in rapidly proliferating, axillary lymph-node negative tumours. In a multivariate analysis LI independently predicted BS (P = 0.08) in rapidly proliferating tumours. LI independently predicted BS in rapidly (P = 0.025) and slowly (P = 0.09) proliferating, axillary lymph-node negative tumours. If the tumours were not categorised according to proliferation rate, LI and outcome were not significantly related. The results clearly confirm the presence of efficient immunological antitumour defence mechanisms in human breast cancer. Consequently tumour-host interactions are subject to further studies particularly in axillary lymph-node negative breast cancer.European Journal of Cancer 02/1992; 28A(4-5):859-64. DOI:10.1016/0959-8049(92)90134-N · 4.82 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Colorectal carcinomas (CRCs) with high microsatellite instability (MSI-H) share clinicopathological features distinctly different from their microsatellite stable (MSS) counterparts. Unlike MSS cancers, MSI-H CRCs occur predominantly in the right-sided colon and are often characterised by a strong lymphocyte infiltration. A poor differentiation pattern is found in most MSI-H CRCs, even though patients with MSI-H carcinomas seem to have a significantly longer survival after surgical resection. To clarify which factors contribute to the obvious paradoxon of a more favourable prognosis of MSI tumours, several clinical and histopathological features as well as the microsatellite status were evaluated in 120 colorectal cancer cases fulfilling clinical criteria (Bethesda) indicative for familial colorectal cancer. Microsatellite instability status and lymphocyte infiltration were related to tumour stage and patients' follow-up. Statistical analysis confirmed well-known relations, such as enhanced lymphocyte infiltration accompanied by Crohn's like reaction (CLR) in MSI-H cancers (CLR+ in 27 out of 47 MSI-H vs 14 out of 71 MSS CRCs, P<0.001). However, after stratification for depth of local invasion and penetration of the primary tumour, T3 tumours displaying MSI had a significantly lower rate of distant metastases (M1 in four out of 35 MSI-H vs 20 out of 41 MSS CRCs, P<0.001). A similar tendency was observed for CLR-positive CRCs (M1 in six out of 29 CLR+ vs 17 out of 45 CLR- CRCs, P=0.13). In a logistic regression model, the MSI-H phenotype and the presence of CLR were independent predictors of a low UICC stage (P=0.006 and 0.04, respectively). These data, together with the recent definition of highly immunogenic neo-antigens expressed in MSI-H tumour cells, suggest that MSI-H CRCs elicit a protective host response that may prevent metastasis formation.British Journal of Cancer 06/2005; 92(9):1746-53. DOI:10.1038/sj.bjc.6602534 · 4.82 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
[Show abstract] [Hide abstract]
ABSTRACT: The purpose of this study was to clarify whether HLA-DR expression of colorectal tumour cells or the CD4+/CD8+ ratio of the tumour infiltrating lymphocytes is significantly associated with the prognosis of colorectal cancer. Using flow cytometry, we studied the tumour cell expression of the HLA class II in 70 enzymatically dissociated colorectal cancers and the phenotype of tumour infiltrating lymphocytes (TILs) in 41 cases. There was no trend in 5-year survival between three levels (low, medium, high) of HLA-DR expression on the tumour cells. Patients with low CD4+/CD8+ ratios had a better clinical course, with significantly higher 5-year survival, p=0.046, independent of the Dukes stage and age. Our results have implications for tumour immunology; colorectal cancer cells might be a target for cytotoxic T-lymphocytes, however the tumour cells are not able to initiate an immune response. Stimulation of the immune system could possible be obtained using dendritic cells cultured in vitro and loaded with tumour antigens.Cancer Immunology and Immunotherapy 08/2003; 52(7):423-8. DOI:10.1007/s00262-003-0388-5 · 3.94 Impact Factor