Abstract

IntroductionCellular immune response to cancer is known to be of great importance for tumor control. Moreover, solid tumors influence circulating lymphocytes, which has been shown for several types of cancer. In our prospective study we elucidate changes in lymphocyte subsets in patients with colorectal carcinoma compared to healthy volunteers.MethodsFlow cytometry was performed at diagnosis of colon carcinoma to analyze B cells, T cells and NK cells including various subtypes of each group. Univariate and multivariate analyses including age, gender, tumor stage, sidedness and microsatellite instability status (MSI) were performed.ResultsForty-seven patients and 50 healthy volunteers were included. Median age was 65 years in patients and 43 years in the control group. Univariate analysis revealed lower total lymphocyte counts, lower CD4 + cells, CD8 + cells, B cells and NKs including various of their subsets in patients. In multivariate analysis patients had inferior values of B cells, CD4 + cells and NK cells and various subsets, regardless of age and gender. Naïve, central memory and HLADR + CD8 + cells showed an increase in patients whereas all other altered subsets declined. MSI status had no influence on circulating lymphocytes except for higher effector memory CD8 + cells in MSI-high patients. Localization in the left hemicolon led to higher values of total cytotoxic T cells and various T cell subsets.ConclusionWe found significant changes in circulating lymphocyte subsets in colon carcinoma patients, independent of physiological alterations due to gender or age. For some lymphocyte subsets significant differences according to tumor localization or MSI-status could be seen.

Highlights

  • Cellular immune response to cancer is known to be of great importance for tumor control

  • For patients with colorectal carcinoma few studies exist regarding alterations of lymphocytes and their subsets compared to healthy controls and most of them focus on circulating immune factors as cytotoxic T lymphocyte antigen 4 (CTLA-4) or expression levels of certain cytotoxicity receptors on NK cells and not on lymphocyte subsets [5, 6]

  • Colorectal carcinoma patients presented with significantly lower values of absolute circulating B cell, T cell (CD4 + and CD8 +) and NK cell counts including various subsets compared to healthy volunteers in univariate analysis

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Summary

Introduction

Cellular immune response to cancer is known to be of great importance for tumor control. For patients with colorectal carcinoma few studies exist regarding alterations of lymphocytes and their subsets compared to healthy controls and most of them focus on circulating immune factors as cytotoxic T lymphocyte antigen 4 (CTLA-4) or expression levels of certain cytotoxicity receptors on NK cells and not on lymphocyte subsets [5, 6]. The localization of the tumor in the right or left hemicolon harbors different molecular and phenotypic characteristics including differences in immunogenicity [14, 15] The influence of these factors has hardly been considered when regarding the cellular immune system of cancer patients. The aim of our study was to elucidate changes in total peripheral lymphocyte counts, B cells, T cells and NK cells with various subsets as well as the impact of age, gender, MSI status and tumor sidedness in patients with localized and metastasized colorectal cancer compared to healthy individuals

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