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20 pages, 7548 KiB

Open AccessArticle

Ultrafine Jujube Powder Enhances the Infiltration of Immune Cells during Anti-PD-L1 Treatment against Murine Colon Adenocarcinoma

by Nan Jing, Luoyang Wang, Huiren Zhuang, Guoqiang Jiang and Zheng Liu

Cancers 2021, 13(16), 3987; https://doi.org/10.3390/cancers13163987 - 7 Aug 2021

Cited by 13 | Viewed by 3629

Abstract

Whereas dietary intervention with natural nutrients plays an important role in activating the immune response and holds unprecedented application potential, the underpinning mechanism is poorly understood. The present work was dedicated to comprehensively examine the effects of ultrafine jujube powder (JP) on the [...] Read more.

Whereas dietary intervention with natural nutrients plays an important role in activating the immune response and holds unprecedented application potential, the underpinning mechanism is poorly understood. The present work was dedicated to comprehensively examine the effects of ultrafine jujube powder (JP) on the gut microbiota and, consequentially, the effects associated with the response rate to anti-PD-L1 treatment against murine colon adenocarcinoma. A murine colon adenocarcinoma model with anti-PD-L1 immunotherapy was established to evaluate how dietary interventions affect the microbiota. In vitro and in vivo experiments confirmed the role of SCFAs in the immune response. Oral administration of JP greatly improves the response of anti-PD-L1 treatment against murine colon adenocarcinoma. Such an improvement is associated with the alteration of gut microbiota which leads to an increased abundance of Clostridiales, including Ruminococcaceae and Lachnospiraceae, an elevated SCFA production, and an intensified infiltration of CD8⁺ T cells to the tumor microenvironment. This work demonstrates that JP is particularly effective in modulating the gut microbiota for an improved immune checkpoint blockage therapy by boosting cytotoxic CD8⁺ T cells in tumor-infiltrating lymphocytes. The experimental findings of the present study are helpful for the development of dietary intervention methods for cancer immunotherapy using natural nutrients. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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18 pages, 2771 KiB

Open AccessArticle

Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice

by William J. Turbitt, Shannon K. Boi, Justin T. Gibson, Rachael M. Orlandella and Lyse A. Norian

Cancers 2021, 13(10), 2295; https://doi.org/10.3390/cancers13102295 - 11 May 2021

Cited by 3 | Viewed by 2602

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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12 pages, 444 KiB

Open AccessArticle

Immunonutrition Changes Inflammatory Response in Colorectal Cancer: Results from a Pilot Randomized Clinical Trial

by Mateusz Wierdak, Marcin Surmiak, Katarzyna Milian-Ciesielska, Mateusz Rubinkiewicz, Anna Rzepa, Michał Wysocki, Piotr Major, Stanisław Kłęk and Michał Pędziwiatr

Cancers 2021, 13(6), 1444; https://doi.org/10.3390/cancers13061444 - 22 Mar 2021

Cited by 15 | Viewed by 3625

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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15 pages, 2810 KiB

Open AccessArticle

Immune Responses Raised in an Experimental Colon Carcinoma Model Following Oral Administration of Lactobacillus casei

by Georgios Aindelis, Angeliki Tiptiri-Kourpeti, Evangeli Lampri, Katerina Spyridopoulou, Eleftheria Lamprianidou, Ioannis Kotsianidis, Petros Ypsilantis, Aglaia Pappa and Katerina Chlichlia

Cancers 2020, 12(2), 368; https://doi.org/10.3390/cancers12020368 - 5 Feb 2020

Cited by 61 | Viewed by 5067

Abstract

The role of dietary probiotic strains on host anti-cancer immune responses against experimental colon carcinoma was investigated. We have previously shown that Lactobacillus casei administration led to tumor growth suppression in an experimental colon cancer model. Here, we investigated the underlying immune mechanisms [...] Read more.

The role of dietary probiotic strains on host anti-cancer immune responses against experimental colon carcinoma was investigated. We have previously shown that Lactobacillus casei administration led to tumor growth suppression in an experimental colon cancer model. Here, we investigated the underlying immune mechanisms involved in this tumor-growth inhibitory effect. BALB/c mice received daily live lactobacilli per os prior to the establishment of a syngeneic subcutaneous CT26 tumor. Tumor volume, cytokine production, T cell differentiation and migration, as well as tumor cell apoptosis were examined to outline potential immunomodulatory effects following L. casei oral intake. Probiotic administration in mice resulted in a significant increase in interferon gamma (IFN-γ), Granzyme B and chemokine production in the tumor tissue as well as enhanced CD8⁺ T cell infiltration, accompanied by a suppression of tumor growth. Cytotoxic activity against cancer cells was enhanced in probiotic-fed compared to control mice, as evidenced by the elevation of apoptotic markers, such as cleaved caspase 3 and poly (ADP-ribose) polymerase 1 (PARP1), in tumor tissue. Oral administration of Lactobacillus casei induced potent Th1 immune responses and cytotoxic T cell infiltration in the tumor tissue of tumor-bearing mice, resulting in tumor growth inhibition. Thus, the microorganism may hold promise as a novel dietary immunoadjuvant in raising protective anti-cancer immune responses. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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Review

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18 pages, 360 KiB

Open AccessReview

Dietary Polyphenols: Promising Adjuvants for Colorectal Cancer Therapies

by Laura Bracci, Alessia Fabbri, Manuela Del Cornò and Lucia Conti

Cancers 2021, 13(18), 4499; https://doi.org/10.3390/cancers13184499 - 7 Sep 2021

Cited by 22 | Viewed by 3682

Abstract

Colorectal cancer (CRC) is a major cancer type and a leading cause of death worldwide. Despite advances in therapeutic management, the current medical treatments are not sufficient to control metastatic disease. Treatment-related adverse effects and drug resistance strongly contribute to therapy failure and [...] Read more.

Colorectal cancer (CRC) is a major cancer type and a leading cause of death worldwide. Despite advances in therapeutic management, the current medical treatments are not sufficient to control metastatic disease. Treatment-related adverse effects and drug resistance strongly contribute to therapy failure and tumor recurrence. Combination therapy, involving cytotoxic treatments and non-toxic natural compounds, is arousing great interest as a promising more effective and safer alternative. Polyphenols, a heterogeneous group of bioactive dietary compounds mainly found in fruit and vegetables, have received great attention for their capacity to modulate various molecular pathways active in cancer cells and to affect host anticancer response. This review provides a summary of the most recent (i.e., since 2016) preclinical and clinical studies using polyphenols as adjuvants for CRC therapies. These studies highlight the beneficial effects of dietary polyphenols in combination with cytotoxic drugs or irradiation on both therapy outcome and drug resistance. Despite substantial preclinical evidence, data from a few pilot clinical trials are available to date with promising but still inconclusive results. Larger randomized controlled studies and polyphenol formulations with improved bioavailability are needed to translate the research progress into clinical applications and definitively prove the added value of these molecules in CRC management. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

17 pages, 679 KiB

Open AccessReview

Diet as a Potential Moderator for Genome Stability and Immune Response in Pediatric Leukemia

by Shanshan Wang, Christopher A. Maxwell and Neha M. Akella

Cancers 2021, 13(3), 413; https://doi.org/10.3390/cancers13030413 - 22 Jan 2021

Cited by 3 | Viewed by 5496

Abstract

Pediatric leukemias are the most prevalent cancers affecting children in developed societies, with childhood acute lymphoblastic leukemia (ALL) being the most common subtype. As diet is a likely modulator of many diseases, this review focuses on the potential for diet to influence the [...] Read more.

Pediatric leukemias are the most prevalent cancers affecting children in developed societies, with childhood acute lymphoblastic leukemia (ALL) being the most common subtype. As diet is a likely modulator of many diseases, this review focuses on the potential for diet to influence the incidence and progression of childhood ALL. In particular, the potential effect of diets on genome stability and immunity during the prenatal and postnatal stages of early childhood development are discussed. Maternal diet plays an integral role in shaping the bodily composition of the newborn, and thus may influence fetal genome stability and immune system development. Indeed, higher birth weights of newborns are associated with increased risk of ALL, which suggests in-utero biology may shape the evolution of preleukemic clones. Postnatally, the ingestion of maternal breastmilk both nourishes the infant, and provides essential components that strengthen and educate the developing immune system. Consistently, breast-feeding associates with decreased risk of ALL development. For children already suffering from ALL, certain dietary regimens have been proposed. These regimens, which have been validated in both animals and humans, alter the internal hormonal environment. Thus, hormonal regulation by diet may shape childhood metabolism and immunity in a manner that is detrimental to the evolution or expansion of preleukemic and leukemic ALL clones. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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18 pages, 1121 KiB

Open AccessFeature PaperReview

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

by Sandra Gessani and Filippo Belardelli

Cancers 2021, 13(2), 196; https://doi.org/10.3390/cancers13020196 - 7 Jan 2021

Cited by 12 | Viewed by 3355

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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32 pages, 1785 KiB

Open AccessReview

Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development

by Antimo Cutone, Giusi Ianiro, Maria Stefania Lepanto, Luigi Rosa, Piera Valenti, Maria Carmela Bonaccorsi di Patti and Giovanni Musci

Cancers 2020, 12(12), 3806; https://doi.org/10.3390/cancers12123806 - 17 Dec 2020

Cited by 25 | Viewed by 10564

Abstract

The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne [...] Read more.

The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne mutagens, dysbalance of intestinal microbiome composition and chronic intestinal inflammation, with loss of intestinal epithelial barrier and enhanced cell proliferation rate. Therapies aimed at shutting down mucosal inflammatory response represent the foundation for IBDs treatment. However, when applied for long periods, they can alter the immune system and promote microbiome dysbiosis and carcinogenesis. Therefore, it is imperative to find new safe substances acting as both potent anti-inflammatory and anti-pathogen agents. Lactoferrin (Lf), an iron-binding glycoprotein essential in innate immunity, is generally recognized as safe and used as food supplement due to its multifunctionality. Lf possesses a wide range of immunomodulatory and anti-inflammatory properties against different aseptic and septic inflammatory pathologies, including IBDs. Moreover, Lf exerts anti-adhesive, anti-invasive and anti-survival activities against several microbial pathogens that colonize intestinal mucosa of IBDs patients. This review focuses on those activities of Lf potentially useful for the prevention/treatment of intestinal inflammatory pathologies associated with colorectal cancer development. Full article

(This article belongs to the Special Issue Diet and Anti-Cancer Immune Response)

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