ABSTRACT
Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.
Subject(s)
Colorectal Neoplasms , Granzymes , Interferon-gamma , Killer Cells, Natural , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/blood , Male , Female , Middle Aged , Interferon-gamma/metabolism , Aged , Granzymes/metabolism , Perforin/metabolism , CD56 Antigen/metabolism , Flow Cytometry , AdultABSTRACT
Adaptive immune cells prevent solid tumor progression by targeting and killing tumor cells. However, there are no comprehensive studies on peripheral circulating adaptive immune cell characterization in colorectal cancer (CRC) patients or the effect of tumor-node-metastasis (TNM) stages on these cells. In this study, the number, phenotype, and function of different subsets of circulating adaptive immune cells in peripheral blood of CRC patients were analyzed. We found remarkable differences in CRC patients compared with those in healthy controls, including reduced absolute counts of total T cells, helper T lymphocytes (Th), cytotoxic T lymphocytes (Tc), and double-negative T lymphocytes, a decreased proportion of INF-γ+ cells in total T cells and Th, and increased percentages of B cells, plasmablasts, and activated T cells. Compared with early-stage CRC patients, advanced-stage CRC patients showed more severe immunosenescence, which manifested as decreased proportions of CD8+ naive T cells with strong proliferative ability and CD8+ central memory T cells with immune surveillance function. Proportions and absolute counts of CD8+ and CD4+ terminally differentiated effector memory T cells were increased, indicating immunosenescence. The immune cell characteristics analyzed in this study serve as a starting point for further research to determine potential clinical implications.