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Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy.

ABSTRACT: Metabolism reprogramming is critical for both cancer progression and effective immune responses in the tumor microenvironment. Amino acid metabolism in different cells and their cross-talk shape tumor immunity and therapy efficacy in patients with cancer. In this review, we focus on multiple amino acids and their transporters, solute carrier (SLC) members. We discuss their involvement in regulation of immune responses in the tumor microenvironment and assess their associations with cancer immunotherapy, chemotherapy, and radiation therapy, and we review their potential as targets for cancer therapy. We stress the necessity to understand individual amino acids and their transporters in different cell subsets, the molecular intersection between amino acid metabolism, and effective T cell immunity and its relevance in cancer therapies.

SUBMITTER: Wang W

PROVIDER: S-EPMC7655528 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy.

Wang Weimin W Zou Weiping W

Molecular cell 20200929 3

Metabolism reprogramming is critical for both cancer progression and effective immune responses in the tumor microenvironment. Amino acid metabolism in different cells and their cross-talk shape tumor immunity and therapy efficacy in patients with cancer. In this review, we focus on multiple amino acids and their transporters, solute carrier (SLC) members. We discuss their involvement in regulation of immune responses in the tumor microenvironment and assess their associations with cancer immuno ...[more]

PMID: 32997964

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Project description:Pigs exposed to heat stress (HS) increase body temperature in which can damage the intestinal epithelia and affect the absorption and availability of amino acids (AA). Protein digestion and metabolism further increase body temperature. An experiment was conducted with six pairs of pigs (of 47.3 ± 1.3 kg initial body weight) exposed to natural HS to assess the effect of substituting dietary protein-bound AA by free AA on morphology and gene expression of intestinal epithelial and serum concentration (SC) of free AA. Treatments were: high protein, 21.9% crude protein (CP) diet (HShp) and low protein, 13.5% CP diet supplemented with crystalline Lys, Thr, Met, Trp, His, Ile, Leu, Phe, and Val (HSaa). The HShp diet met or exceeded all AA requirements. The HSaa diet was formulated on the basis of ideal protein. Pigs were fed the same amount at 0700 and 1900 hours during the 21-d study. Blood samples were collected at 1700 hours (2.0 h before the evening meal), 2030 hours, and 2130 hours (1.5 and 2.5 h after the evening meal). At the end, all pigs were sacrificed to collect intestinal mucosa and a 5-cm section from each segment of the small intestine from each pig. Villi measures, expression of AA transporters (y+L and B0) in mucosa, and SC of AA were analyzed. Ambient temperature fluctuated daily from 24.5 to 42.6 °C. Weight gain and G.F were not affected by dietary treatment. Villi height tended to be larger (P ≤ 0.10) and the villi height:crypt depth ratio was higher in duodenum and jejunum of pigs fed the HSaa diet (P < 0.05). Gene expression of transporter y+L in jejunum tended to be lower (P < 0.10) and transporter B0 in the ileum was lower (P < 0.05) in HSaa pigs. Preprandial (1700 hours) SC of Arg, His, Ile, Leu, Thr, Trp, and Val was higher (P < 0.05), and Phe tended to be higher (P < 0.10) in HShp pigs. At 2030 hours (1.5 h postprandial), serum Lys, Met, and Thr were higher in the HSaa pigs (P < 0.05). At 2130 hours (2.5 h), Arg, His, Ile, Phe, and Trp were lower (P < 0.05); Met was higher (P < 0.05); and Lys tended to be higher (P < 0.10) in HSaa pigs. In conclusion, feeding HS pigs with low protein diets supplemented with free AA reduces the damage of the intestinal epithelia and seems to improve its absorption capacity, in comparison with HS pigs fed diets containing solely protein-bound AA. This information is useful to formulate diets that correct the reduced AA consumption associated with the decreased voluntary feed intake of pigs under HS.

Project description:Dietary amino acids (AA) supplied as protein or in free form are not only digested and absorbed at different rates but can also induce differences in the intestinal physiology of pigs. We compared the apparent jejunal AA digestibility, intestinal morphology, and gene expression of AA transporters of pigs fed diets providing different forms of AA. Thirty growing pigs (33.7 ± 4.1 kg) were fed one of three experimental diets that provided AA either as protein from feather meal (INT), as free AA and small peptides obtained by extensive acid hydrolysis of feathers (HYD), or as a mix of individual purified AA with the same AA profile as HYD (FAA). Pigs were fed the same quantity of feed, energy, and AA. After 14 d, pigs were slaughtered 3 h after feeding a meal with indigestible markers. Digesta and tissue were collected from different sections of the small intestine. Jejunal digesta was used to measure apparent jejunal digestibility of AA. Samples of the duodenum, jejunum, and ileum were used to measure intestinal morphology and the gene expression of intestinal AA transporters. The measured apparent jejunal digestibility of AA of INT was lower compared to HYD and FAA (P < 0.05). The apparent jejunal digestibility of Cys, Gly, His, Met, and Pro was lower for FAA compared to HYD (P < 0.05). This may be due to the small peptides in HYD, which are absorbed faster than individual AA. The villi area in the ileum of HYD fed pigs was the highest (P < 0.05) among the treatments, which may be associated with the reabsorption of endogenous proteins, which occurs mostly in the ileum. In the duodenum, HYD and FAA had lower expression of PepT1 (P < 0.01) probably due to the rapid transit time of digesta compared to INT fed pigs. Pigs fed HYD expressed more ASCT2 (P = 0.02) and CAT-1 (P = 0.04) in the jejunum compared to the pigs fed the other diets. The expression of these transporters along the intestine depended on the relative abundance of readily absorbable dietary AA. Results showed that dietary AA form can have an influence on the morphology and on the expression of different AA transporters along the different sections of the small intestine.

Dataset Information

Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy.

Publications

Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy.

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