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Colorectal cancer (CRC) is a leading cause of death worldwide. Despite advances in surgical and therapeutic management, tumor metastases and resistance to therapy still represent major hurdles. CRC risk is highly modifiable by lifestyle factors, including diet, which strongly influences both cancer incidence and related mortality. Galectin-3 (Gal-3) is a multifaceted protein involved in multiple pathophysiological pathways underlying chronic inflammation and cancer. Its versatility is given by the ability to participate in a wide range of tumor-promoting processes, including cell–cell/cell–matrix interactions, cell growth regulation and apoptosis, and the immunosuppressive tumor microenvironment. This review provides an updated summary of preclinical and observational human studies investigating the pathogenetic role of Gal-3 in intestinal inflammation and CRC, as well as the potential of Gal-3 activity inhibition by plant-source food-derived bioactive compounds to control CRC onset/growth. These studies highlight both direct and immuno-mediated effects of Gal-3 on tumor growth and invasiveness and its potential role as a CRC prognostic biomarker. Substantial evidence indicates natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. However, critical issues, such as their bioavailability and efficacy, in controlled human studies need to be addressed to translate research progress into clinical applications.

Type I interferons (IFN-I) are antiviral cytokines endowed with multiple biological actions, including antitumor activity. Studies in mouse models and cancer patients support the concept that endogenous IFN-I play important roles in the control of tumor development and growth as well as in response to several chemotherapy/radiotherapy treatments. While IFN-I signatures in the tumor microenvironment are often considered as biomarkers for a good prognostic response to antitumor therapies, prolonged IFN-I signaling can lead to immune dysfunction, thereby promoting pathogen or tumor persistence, thus revealing the “Janus face” of these cytokines in cancer control, likely depending on timing, tissue microenvironment and cumulative levels of IFN-I signals. Likewise, IFN-I exhibit different and even opposite effects on obesity, a pathologic condition linked to cancer development and growth. As an example, evidence obtained in mouse models shows that localized expression of IFN-I in the adipose tissue results in inhibition of diet–induced obesity, while hyper-production of these cytokines by specialized cells such as plasmacytoid dendritic cells in the same tissue, can induce systemic inflammatory responses leading to obesity. Further studies in mouse models and humans should reveal the mechanisms by which IFN-I can regulate both tumor growth and obesity and to understand the role of factors such as genetic background, diet and microbioma in shaping the production and action of these cytokines under physiological and pathological conditions.

β-glucans represent a heterogeneous group of naturally occurring and biologically active polysaccharides found in many kinds of edible mushrooms, baker’s yeast, cereals and seaweeds, whose health-promoting effects have been known since ancient times. These compounds can be taken orally as food supplements or as part of daily diets, and are safe to use, nonimmunogenic and well tolerated. A main feature of β-glucans is their capacity to function as biological response modifiers, exerting regulatory effects on inflammation and shaping the effector functions of different innate and adaptive immunity cell populations. The potential to interfere with processes involved in the development or control of cancer makes β-glucans interesting candidates as adjuvants in antitumor therapies as well as in cancer prevention strategies. Here, the regulatory effects of dietary β-glucans on human innate immunity cells are reviewed and their potential role in cancer control is discussed.

Colorectal cancer (CRC), a multi-step malignancy showing increasing incidence in today’s societies, represents an important worldwide health issue. Exogenous factors, such as lifestyle, diet, nutrition, environment and microbiota, contribute to CRC pathogenesis, also influencing non neoplastic cells, including immune cells. Several immune dysfunctions were described in CRC patients at different disease stages. Many studies underline the role of microbiota, obesity-related inflammation, diet and host reactive cells, including dendritic cells (DC), in CRC pathogenesis. Here, we focused on DC, the main cells linking innate and adaptive anti-cancer immunity. Variations in the number and phenotype of circulating and tumor-infiltrating DC have been found in CRC patients and correlated with disease stages and progression. A critical review of DC-based clinical studies and of recent advances in cancer immunotherapy leads to consider new strategies for combining DC vaccination strategies with check-point inhibitors, thus opening perspectives for a more effective management of this neoplastic disease.

Simple Summary: Colorectal cancer (CRC) incidence is increasing worldwide and represents an important health problem.Therapy failure and progression to metastatic disease are major concerns. Among the factors involved in tumor growth, galectin-3 (Gal-3) plays an important role due to its ability to finetune a number of molecular players that act at different levels of cancer-related processes. A clear relationship between Gal-3 and CRC has been demonstrated. Several studies have, indeed, reported a pathogenetic role for this protein in intestinal inflammation and CRC onset/progression. Moreover, some plant-source food-derived bioactive compounds (mostly fibers and polyphenols) can contribute to the control of CRC onset/growth through their capacity to block Gal-3 activities. In this review, we summarize these studies, highlighting the influence of Gal-3 on CRC risk/progression, cancer cell spreading and patient prognosis, as well as the potential of natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. Colorectal cancer (CRC) is a leading cause of death worldwide. Despite advances in surgical and therapeutic management, tumor metastases and resistance to therapy still represent major hurdles. CRC risk is highly modifiable by lifestyle factors, including diet, which strongly influences both cancer incidence and related mortality. Galectin-3 (Gal-3) is a multifaceted protein involved in multiple pathophysiological pathways underlying chronic inflammation and cancer. Its versatility is given by the ability to participate in a wide range of tumor-promoting processes, including cell–cell/cell–matrix interactions, cell growth regulation and apoptosis, and the immunosuppressive tumor microenvironment. This review provides an updated summary of preclinical and observational human studies investigating the pathogenetic role of Gal-3 in intestinal inflammation and CRC, as well as the potential of Gal-3 activity inhibition by plant-source food-derived bioactive compounds to control CRC onset/growth. These studies highlight both direct and immuno-mediated effects of Gal-3 on tumor growth and invasiveness and its potential role as a CRC prognostic biomarker. Substantial evidence indicates natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. However, critical issues, such as their bioavailability and efficacy, in controlled human studies need to be addressed to translate research progress into clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy use has become standard for many patients with advanced kidney cancer; unfortunately, <50% of patients experience durable responses. Mounting evidence suggests that modifiable factors, such as diet and obesity, impact immunotherapy outcomes. Obesity, a major U.S. health epidemic, blunts anti-tumor immunity and promotes tumor growth in multiple preclinical models. However, the full biological impact of obesity on the T cell responses needed to achieve positive immunotherapy outcomes remains unclear. Here, we studied the effects of obesity on T cell responses following combinatorial immunotherapy in a mouse model of kidney cancer. We found that obesity is associated with blunted effector T cell responses, resulting in diminished immunotherapy outcomes. This therapy produces sustained T cell responses and robust tumor control in obese-resistant mice fed the same high-fat diet. Finding ways to amplify T cell responses within renal tumors from hosts with obesity will be critical for achieving optimal immunotherapy outcomes. Associations between modifiable factors and the efficacy of cancer immunotherapies remain uncertain. We found previously that diet-induced obesity (DIO) reduces the efficacy of an immunotherapy consisting of adenovirus-encoded TRAIL plus CpG oligonucleotide (AdT/CpG) in mice with renal tumors. To eliminate confounding effects of diet and determine whether outcomes could be improved in DIO mice, we evaluated AdT/CpG combined with anti-CTLA-4 in diet-matched, obese-resistant (OB-RES) versus DIO tumor-bearing mice. Therapy-treated OB-RES mice displayed effective renal tumor control and sustained CD4+ and CD8+ T cell responses. In contrast, therapy-treated DIO mice exhibited progressive tumor outgrowth and blunted T cell responses, characterized by reduced intratumoral frequencies of IFNγ+ CD4+ and CD8+ T cells. Weak effector T cell responses in therapy-treated DIO mice were accompanied by low intratumoral concentrations of the T cell chemoattractant CCL5, heightened concentrations of pro-tumorigenic GM-CSF, and impaired proliferative capacity of CD44+CD8+ T cells in tumor-draining lymph nodes. Our findings demonstrate that in lean mice with renal tumors, combining in situ T cell priming upstream of anti-CTLA-4 enhances outcomes versus anti-CTLA-4 alone. However, host obesity is associated with heightened immunotherapy resistance, characterized by multi-factorial deficiencies in effector CD4+ and CD8+ T cell responses that extend beyond the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite increased information showing obesity is an important breast cancer (BC) risk factor, the mechanisms implicated in this association are not well understood. In this review we describe multiple lines of evidence indicating that altered secretion of androgens and adipokines, from dysfunctional adipose tissue, are independently linked with BC development. However, adipokines (adiponectin and leptin) participate in important biological processes in BC cells by modulating signaling pathways similar to those used by the androgen receptor. These similarities suggest that crosstalk between these factors can occur, with a high probability that its interactions may be responsible for modifying the behavior of normal and tumor cells, especially in obesity. The knowledge of how adiponectin and leptin can interact with the androgen receptor signaling may prospectively guide the development of therapeutic approaches aimed at potentiating the inhibitory actions of adiponectin and androgen receptor or interfering with the pro-stimulatory role of leptin in BC. Obesity is an increasing health challenge and is recognized as a breast cancer risk factor. Although obesity-related breast cancer mechanisms are not fully understood, this association has been linked to impaired hormone secretion by the dysfunctional obese adipose tissue (hyperplasic and hypertrophic adipocytes). Among these hormones, altered production of androgens and adipokines is observed, and both, are independently associated with breast cancer development. In this review, we describe and comment on the relationships reported between these factors and breast cancer, focusing on the biological associations that have helped to unveil the mechanisms by which signaling from androgens and adipokines modifies the behavior of mammary epithelial cells. Furthermore, we discuss the potential crosstalk between the two most abundant adipokines produced by the adipose tissue (adiponectin and leptin) and the androgen receptor, an emerging marker in breast cancer. The identification and understanding of interactions among adipokines and the androgen receptor in cancer cells are necessary to guide the development of new therapeutic approaches in order to prevent and cure obesity and breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Nutritional support for patients who underwent surgery for colorectal cancer is widely accepted for reducing the incidence of perioperative complications. Immunonutrition is generally recommended to decrease the incidence of infectious complications. However, there is little clinical data regarding the impact of such treatment on tumor biology. Some basic studies show its negative impact on the development of the tumor, while others suggest it might be beneficial. Currently, there is no clinical evidence for any effect of immunonutrition on tumor tissues in vivo. Therefore, we designed this pilot randomized controlled trial to investigate the impact of immunonutrition compared with standard nutritional support in the preoperative period on the inflammatory response, cytokine expression, and leukocyte infiltration in the tumor tissue. Changes in tumor necrosis factor alpha (TNF-α), interleukin 8 or chemokine (C-X-C motif) ligand (CXCL8), and chemokine (C-X-C motif) ligand 1 (CXCL1) expression were observed after the intervention. In the immune group, a decrease in neutrophil infiltration was observed. Immunonutrition in the preoperative period influenced inflammatory response in patients with colorectal cancer. Introduction: Surgery is the first choice of treatment for colorectal cancer. Nutritional support in the form of oral nutritional supplements (ONSs) in the preoperative period is widely accepted for reducing the incidence of perioperative complications, and immunonutrition is generally recommended. However, there is little clinical data regarding the impact of such treatment on tumor biology. Material and Methods: In this study, tumor tissue and blood samples were collected from 26 patients during preoperative colonoscopy at the time of clinical diagnosis (sample A). Group 1 received standard ONSs (3× Nutricia Nutridrink Protein per day) for 2 weeks before surgery. In group 2, immune ONSs (2× Nestle Impact Oral) were administered for the same duration. Tumor tissue (sample B) was then retrieved from the tumor after resection. Changes in the expression levels of inflammatory cytokines (TNF-α, interleukin 8 or chemokine (C-X-C motif) ligand (CXCL8), stromal cell-derived factor 1 (SDF1a), chemokine (C-X-C motif) ligand 6 (CXCL6), chemokine (C-X-C motif) ligand (CXCL2), myeloperoxidase (MPO), and CXCL1) were assessed during the perioperative course. Results: TNF-α expression differed after intervention between the two groups (immune group 31.63 ± 13.28; control group 21.54 ± 6.84; p = 0.049) and prior to and after intervention in the control group (prior to intervention 35.68 ± 24.41; after intervention 21.54 ± 6.84; p = 0.038). Changes in CXCL8 expression in the control group occurred prior to and after intervention (prior to intervention 2975.93 ± 1484.04; after intervention 1584.85 ± 1659.84; p = 0.041). CXCL1 expression was increased in the immune group and decreased in the control group (immune group 2698.27 (1538.14–5124.70); control group 953.75 (457.85–1534.60); p = 0.032). In both groups, a decrease in superficial neutrophil infiltration was observed, but this was only statistically significant in the immune group. There was no impact of the observed differences between the two groups on surgical outcomes (morbidity, length of stay, readmissions). Conclusions: Immunonutrition in the preoperative period compared with standard nutritional support may influence inflammatory cytokine expression and leukocyte infiltration in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) is a molecular indicator of defective DNA mismatch repair (dMMR). MSI/dMMR status is observed in approximately 5% of metastatic colorectal cancers (mCRC) but 10–18% of localized colorectal cancers. MSI/dMMR status is a major predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs). This review presents the current and future challenges of ICIs for patients with MSI/dMMR colorectal cancer. Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10–18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs. In this review, we will present a comprehensive overview of the literature concerning the efficacy of ICIs in MSI/dMMR mCRC, with a focus on new developments in first-line metastatic setting. Then, we will present current and future challenges of immuno-oncology for patients with MSI/dMMR metastatic CRC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), a multi-step malignancy showing increasing incidence in today's societies, represents an important worldwide health issue. Exogenous factors, such as lifestyle, diet, nutrition, environment and microbiota, contribute to CRC pathogenesis, also influencing non neoplastic cells, including immune cells. Several immune dysfunctions were described in CRC patients at different disease stages. Many studies underline the role of microbiota, obesity-related inflammation, diet and host reactive cells, including dendritic cells (DC), in CRC pathogenesis. Here, we focused on DC, the main cells linking innate and adaptive anti-cancer immunity. Variations in the number and phenotype of circulating and tumor-infiltrating DC have been found in CRC patients and correlated with disease stages and progression. A critical review of DC-based clinical studies and of recent advances in cancer immunotherapy leads to consider new strategies for combining DC vaccination strategies with check-point inhibitors, thus opening perspectives for a more effective management of this neoplastic disease. [ABSTRACT FROM AUTHOR]