Sulforaphane activates CD8+ T cells antitumor response through IL-12RB2/MMP3/FasL-induced MDSCs apoptosis'.

BACKGROUND: Extensive attention has been given to the role of myeloid-derived suppressor cells (MDSCs) in driving tumor progression and treatment failure. Preclinical studies have identified multiple agents that eliminate MDSCs. However, none have been authorized in the cliniccal ues due to the safety reasons. In the present study, we investigated the efficacy and mechanism of sulforaphane (SFN) to eliminate MDSCs in the tumor microenvironment (TME). METHODS: We monitored SFN effect on tumor growth and the percents or apoptosis of immune cell subsets in mice models bearing LLC or B16 cells. Flow cytometry, quantitative reverse transcription-PCR, immunohistochemistry, ELISA, immunofluorescence, imaging flow cytometry and western blot were performed to validate the role of SFN on MDSCs function in vivo and in vitro. RNA sequencing was then used to interrogate the mechanisms of how SFN regulated MDSCs function. Tumor xenograft models were established to evaluate the involvement of IL-12RB2/MMP3/FasL induced MDSCs apoptosis in vivo. We verified the effect of SFN on MDSCs and CD8+ T cells in the blood samples from a phase I clinical trial (KY-2021-0350). RESULTS: In this study, we elucidated that SFN liberated CD8+ T-cell antitumor ability by reducing MDSCs abundance, leading to repressed tumor growth. SFN treatment suppressed MDSCs accumulation in the peripheral blood and tumor sites of mice, but had no effect on the bone marrow. Mechanistically, SFN activates IL-12RB2, which stimulates the MMP3/FasL signaling cascade to trigger caspase 3 cleavage and induce apoptosis in MDSCs. Clinically, SFN treatment eliminates peripheral MDSCs and increases the percentage and activation of CD8+ T cells. CONCLUSIONS: Collectively, we uncovered the role of SFN in eliminating MDSCs to emancipate CD8+ T cells through IL-12RB2/MMP3/FasL induced apoptosis, thus providing a strategy for targeting MDSCs to control tumors and improve clinical efficacy.

Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis.

Background: Despite increasing evidence that has shown the association of ultra-processed foods (UPFs) with cancer risk, the results remain inconclusive. We, therefore, conducted the meta-analysis to clarify the association by including recently published studies. Methods: A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies from inception to January 2023. To pool data, fixed-effects or random-effects models were used where appropriate. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. Results: A total of 13 studies (4 cohort studies and 9 case-control studies) were included in the analysis, with a total of 625,738 participants. The highest UPFs consumption was associated with increased risk of colorectal cancer (OR = 1.23, 95% CI: 1.10-1.38), colon cancer (OR = 1.25, 95% CI: 1.14-1.36), and breast cancer (OR = 1.10, 95% CI: 1.00-1.20) but not rectal cancer (OR = 1.18, 95% CI: 0.97-1.43) and prostate cancer (OR = 1.03, 95% CI: 0.93-1.12). In addition, the subgroup analyses showed that a positive association between UPFs consumption and colorectal cancer was observed among men (OR = 1.31, 95% CI: 1.15-1.50), whereas no significant association was observed among women (OR = 1.10, 95% CI: 0.94-1.29). Conclusion: The present meta-analysis suggests that high UPFs consumption is associated with a significantly increased risk of certain site-specific cancers, especially the digestive tract and some hormone-related cancers. However, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Clinical Correlation of Function and TCR vß Diversity of MAGE-C2-Specific CD8+ T Cell Response in Esophageal Cancer.

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2-specific CD8+ T cells and the relationship of its TCR ß-chain V region (TCR vß) subfamily distribution to prognosis of patients with esophageal cancer. PBMCs and tumor-infiltrating lymphocytes expanded by CD3/CD28 Dynabeads and MAGE-C2 peptides in vitro resulted in the induction of lysosome-associated membrane protein-1 (LAMP-1 or CD107a) on the cell surface and the production of IFN-γ by MAGE-C2-specific CD8+ T cells. We found differential TCR vß subfamily distribution among flow-sorted CD107a+IFN-γ+ and CD107a-IFN-γ- CD8+ T cells. The proportion of CD107a+ and/or IFN-γ+ tetramer+ CD8+ T cells was lower in patients with lymph node metastasis, late tumor stage, and poorly differentiated state (p < 0.05). T-box transcription factor was positively correlated with CD107a and IFN-γ. Kaplan-Meier analysis showed that patients whose MAGE-C2-specific CD8+ T cells expressed high CD107a and/or IFN-γ had a longer survival time when compared with patients whose MAGE-C2-specific CD8+ T cells expressed low levels of CD107a and/or IFN-γ. Moreover, analysis of TCR vß subfamily distribution revealed that a higher frequency of TCR vß16 in MAGE-C2-specific CD8+ T cells was positively correlated with a better prognosis. These results suggest that the presence of functional MAGE-C2-specific CD8+ T cells had an independent prognostic impact on the survival of patients with esophageal cancer.

Dietary patterns and sarcopenia in a Chinese population.

BACKGROUND AND OBJECTIVES: Malnutrition is implicated as a key modifiable risk factor for sarcopenia. As such, a dietary pattern analysis, rather than an analysis of single food items or nutrients, may provide insights into the comprehensive contribution of diet and nutrition to the risk of sarcopenia. Accordingly, the aim of this study was to evaluate the relationships between main dietary patterns and sarcopenia. METHODS AND STUDY DESIGN: A total of 591 participants aged over 40 years were included in this cross-sectional study. A validated food-frequency questionnaire was used to assess their dietary intake, and principal component analysis (PCA) was used to identify the main dietary patterns. A multivariate logistic regression model was used to explore the associations between their main dietary patterns and the risk of sarcopenia. RESULTS: This study identified 56 cases of sarcopenia, equating to an overall detection rate of 9.48%. The PCA revealed four major dietary patterns among the participants: "coarse cereals and vegetables"; "beverages and animal organs"; "poultry, fish and shrimp"; and "fruits and pasta". After adjusting for age, sex, physical activity and smoking, individuals with the "coarse cereals and vegetables" dietary pattern had a 63.0% reduction in the risk of sarcopenia. CONCLUSIONS: The "coarse cereals and vegetables" dietary pattern is negatively correlated with sarcopenia, and may reduce the risk of sarcopenia.

Effect of whole-course nutrition management on patients with esophageal cancer undergoing concurrent chemoradiotherapy: A randomized control trial.

OBJECTIVES: Malnutrition is the most common complication of patients with esophageal cancer and can lead to poor prognosis and death. Good nutritional status has been shown to help improve patient outcomes and reduce complications. In the absence of specific evidence on the effect of nutrition in patients with esophageal cancer, the purpose of this study was to investigate the effect of whole-course nutrition management on the prognosis and complications of chemoradiotherapy in patients with esophageal cancer through a randomized controlled trial. METHODS: A total of 96 patients with esophageal cancer treated with concurrent chemoradiation were randomized to an intervention group (treated with whole-course nutrition management from the Nutrition Support Team) and a control group (treated with the general nutritional method) for approximately 6 wk. Dietary surveys and body measurements were conducted at baseline and every day thereafter. Patient-generated Subjective Global Assessment score, blood index, quality of life, and psychological condition were assessed at baseline and every week before discharge. Complications (e.g., radiation esophagitis, myelosuppression, and skin symptoms), completion rates of therapy, short-term efficacy evaluation, as well as clinical outcomes were measured. RESULTS: A total of 85 patients completed the study (intervention group = 45; control group = 40). There were significant differences in the changes of serum albumin and total protein between the two groups throughout the trial (P < 0.05). Complications (e.g., radioactive esophagitis, skin symptom of complications) and quality of life were statistically different before and after the intervention (P < 0.05). The difference in the change of other indicators was not statistically significant. CONCLUSIONS: Whole-course nutrition management can improve the nutritional status of patients with esophageal cancer treated with concurrent chemoradiotherapy, reduce the severity of radiation esophagitis and radiation skin reactions, improve the quality of life, and relieve depressive symptoms.