In contrast to many cancers, a high infiltration of macrophages in colorectal cancer (CRC) has been associated with improved prognosis for patients. Cytokines and other stimuli from the tumor microenvironment affect monocyte to macrophage maturation and subsequent phenotype and function. Heterogeneous myeloid populations were identified using a novel flow cytometry panel in both tumor and paired non-tumor bowel (NTB) from CRC patients. The frequency of macrophage subsets with a gut-conditioned phenotype was lower in tumor compared with NTB. We used an in vitro system to show that two of the macrophage populations represented pro-inflammatory and anti-inflammatory phenotypes. Conditioned media that contained high levels of interleukin-6 promoted and maintained an anti-inflammatory phenotype in vitro. This study demonstrates the plasticity and heterogeneity of macrophage subtypes in human CRC, and the feasibility of studying complex populations. Ex vivo experiments demonstrate that macrophage subsets are influenced by the tumor microenvironment.

Crohn's disease (CD) is an inflammatory bowel disease characterized by patchy inflammation of the gastrointestinal tract. Ankylosing spondylitis (AS) is primarily characterized by inflammation of the lower vertebral column, and many patients with AS present with inflammatory gut symptoms. Genome-wide association studies have highlighted significant overlap in short nucleotide polymorphisms for both diseases. We hypothesized that patients with CD and AS have a common intestinal immune signature, characterized by inflammatory T cells, compared with healthy people. We designed a pilot study to determine both the feasibility of defining complex immune signatures from primary tissue, and differences in the local immune signature of people with inflammatory diseases compared with healthy people. Intestinal biopsies were obtained by colonoscopy from healthy patients, non-inflamed regions of CD patients and AS patients with inflammatory gut symptoms. A flow cytometry platform was developed measuring polyfunctional T-cell populations based on cytokines, surface molecules and transcription factors. There was overlap in the immune signature of people with CD or AS, characterized by changes in the frequency of regulatory T cells, compared with healthy people. There were significant differences in frequencies of other polyfunctional T-cell populations-CD patients had an increased frequency of T cells producing interleukin-22 (IL-22) and interferon-γ, whereas AS patients had an increased frequency of T cells producing IL-2; compared with healthy people. These data indicate that the local immune signature could be described in these patients and that distinct immune mechanisms may underlie disease progression.

Crohn's disease and ulcerative colitis, collectively referred to as inflammatory bowel diseases (IBD), are the result of an aberrant immune response to ubiquitous antigens in a genetically susceptible host. In the past, treatment has focused on immunosuppression with the aim of achieving symptom-free remission. Over the last two decades, with a better understanding of the underlying pathomechanisms and an increased knowledge of the natural disease course, mucosal healing (the endoscopic absence of visible inflammation) has become the target of therapy. Anti-tumor necrosis factor (TNF)-α therapy was introduced in the late 1990s and, for the first time, targeted and effective medication became available. However, these medications are not without significant side effects, and long-term efficacy is only achieved in about one third of patients. Alongside anti-TNF-α agents, a variety of other drugs targeting different aspects of the immune system will become available over the next few years. This review aims to provide a brief summary of immunologic pathways involved in IBD and shows where current and new drugs fit into these pathways.

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Infiltration of macrophages in colorectal cancer is associated with patient prognosis. Using multiparameter flow cytometry, multiple distinct macrophage populations were detected in tumour tissue recovered from colorectal cancer patients, highlighting the heterogeneity of myeloid populations within complex tissues. Population frequencies of five key macrophage populations were assessed in tumour and matched non-transformed bowel tissue to reveal specific changes caused by the direct presence of the tumour. The frequency of conventional (pro-inflammatory) macrophages (CD45+CD11b+CD33-CD64+CD14-CD206+CD163-) was significantly increased in tumour tissue compared to healthy bowel tissue. This population was analogous to pro-inflammatory IL-12-producing macrophages derived in vitro from blood. A large population of gut resident macrophages was also observed in both tumour and control bowel tissue. “Homeostatic” gut resident macrophages (CD45+CD33+CD14-CD11b-CD64-) and “inflammatory” gut resident macrophages (CD45+CD33+CD14+CD11b+CD64+) were decreased and increased, respectively, in tumour tissue compared with healthy bowel tissue of the same patients. This suggests that macrophages provide a pro-inflammatory environment within the tumour tissue and may explain why these cells are often associated with improved patient outcome in colorectal cancer. Data gained from this study could be used for future investigation of macrophages as both prognostic and therapeutic targets.