Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Die Highlights vom Kongress des American College of Cardiology 2024

Im April diskutierten die Herz-Kreislauf-Spezialisten aus der ganzen Welt auf dem  Kongress des American College of Cardiology (ACC) u.a. neue Therapieansätze bei akutem Myokardinfarkt, koronarer Herzerkrankung, kardiogenem Schock oder Aortenklappenstenose. In unserem Kongress-Dossier haben wir für Sie Berichte über die „Late-Breaking Trials“ und andere wichtige Studien zusammengestellt. 
Erweiterte Suche
Anmelden
nach oben
Pathology & Oncology Research
Erschienen in: Pathology & Oncology Research 1/2015

01.01.2015 | Review

Amino Acids and Immune Response: A Role for Cysteine, Glutamine, Phenylalanine, Tryptophan and Arginine in T-cell Function and Cancer?

verfasst von: Angelos K. Sikalidis

Erschienen in: Pathology & Oncology Research | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing mechanisms not completely delineated. Interesting work has investigated how certain amino acids affect the proliferation rate of T-cells as well as their effectiveness in clearing tumors. The role of amino acids cysteine, glutamine, phenylalanine, tryptophan and arginine in immunomodulation and particularly regarding T-cell proliferation and activation is discussed. The redox balance is reported to affect T-cell proliferation via modulation of cysteine availability. In addition antigen presenting cells (APCs), similar to myeloid cells determine the availability of amino acids in the extracellular microenvironment affecting T-cell proliferation and activation. A better mechanistic understanding of T-cell function modulation via amino acid signaling or metabolic properties may be helpful towards optimization of adaptive immunity with implications for cancer prognosis and treatment.
Literatur
1.
Steinke JW, Lawrence MG (2014) T-cell biology in immunotherapy. Ann Allergy Asthma Immunol 112:195–199PubMedCrossRef
2.
Smith KA (2014) Revisiting the first long-term culture of antigen-specific cytotoxic T cells. Front Immunol 5:194PubMedCentralPubMed
3.
Viret C, Janeway CA Jr (1999) MHC and T cell development. Rev Immunogenet 1:91–104PubMed
4.
von Essen MR, Kongsbak M, Geisler C (2012) Mechanisms behind functional avidity maturation in T cells. Clin Dev Immunol 2012:163453
5.
Robinson AT, Miller N, Alexander DR (1993) CD3 antigen-mediated calcium signals and protein kinase C activation are higher in CD45RO+ than in CD45RA+ human T lymphocyte subsets. Eur J Immunol 23(1):61–68PubMedCrossRef
6.
von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Ødum N, Geisler C (2010) Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol 11(4):344–349CrossRef
7.
Ericsson PO, Orchansky PL, Carlow DA, Teh HS (1996) Differential activation of phospholipase C-γ1 and mitogen-activated protein kinase in naïve and antigen-primed CD4 T cells by the peptide/MHC ligand. J Immunol 156(6):2045–2053PubMed
8.
Viganò S, Utzschneider DT, Perreau M, Pantaleo G, Zehn D, Harari A (2012) Functional avidity: a measure to predict the efficacy of effector T cells? Clin Dev Immunol 153863
9.
Ebert PJ, Jiang S, Xie J, Li QJ, Davis MM (2009) An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nat Immunol 10(11):1162–1169PubMedCentralPubMedCrossRef
10.
Garcia Z, Pradelli E, Celli S, Beuneu H, Simon A, Bousso P (2007) Competition for antigen determines the stability of T cell-dentritic cell interactions during clonal expansion. Proc Natl Acad Sci U S A 104(11):4553–4558PubMedCentralPubMedCrossRef
11.
12.
Choi EML, Chen JL, Wooldridge et al (2003) High avidity antigen-specific CTL identified by CD8-idependent tetramer staining. J Immunol 171(10):5116–5123PubMedCrossRef
13.
Xiao Z, Mescher MF, Jameson SC (2007) Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation. J Exp Med 294(11):2667–2677CrossRef
14.
Slifka MK, Whitton JL (2001) Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR. Nat Immunol 2(8):711–717PubMedCrossRef
15.
Rechtsteiner G, Warger T, Hofmann M, Rammensee HG, Schild HJ, Radsak MP (2006) Precursor frequency can compensate for lower TCR expression in T cell competition during priming in vivo. Eur J Immunol 36(10):2613–2623PubMedCrossRef
16.
Sikalidis AK, Lee J-I, Stipanuk MH (2011) Cellular responses to indispensable amino acid deficiency are mediated through the integrated stress response pathway. Amino Acids 41(1):159–171PubMedCentralPubMedCrossRef
17.
Sikalidis AK, Stipanuk MH (2010) Growing rats respond to a sulfur amino acid-deficient diet by phosphorylation of eIF2α and induction of adaptive components of the integrated stress. J Nutr 140(6):1080–1085PubMedCentralPubMedCrossRef
18.
Bella DL, Hirschberger LL, Hosokawa Y, Stipanuk MH (1999) The mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo. Am J Physiol 276 (Endocrin. Metab. 39): E326–E335
19.
Bella DL, Hahn C, Stipanuk MH (1999) The effects of non-sulfur amino acids and of sulfur amino acids on the regulation of hepatic enzymes of cysteine metabolism. Am J Phsyiol 277(Endocrin. Metab. 40): E144-E153
20.
Cresenzi CL, Lee JI, Stipanuk MH (2003) Cysteine is the metabolic signal responsible for dietary regulation of hepatic cysteine dioxygenase and glutamate cysteine ligase in intact rats. J Nutr 133(9):2697–2702PubMed
21.
Yang BH, Wang X, Ren X (2012) Amino acid metabolism related to immune tolerance by MDSCs. Int Rev Immunol 31(3):177–183PubMedCrossRef
22.
Rodríguez PC, Ochoa AC (2006) T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress. Semin Cancer Biol 16(1):66–72PubMedCrossRef
23.
Levring TB, Hansen AK, Nielsen BL, Kongsbak M, von Essen MR, Woetmann A, Odum N, Bonefeld CM, Geisler C (2012) Activated human CD4+ T cells express transporters for both cysteine and cystine. Sci Rep 2:266PubMedCentralPubMedCrossRef
24.
Srivastava MK, Sinha P, Clements VK, Rodriguez P, Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 70(1):68–77PubMedCentralPubMedCrossRef
25.
26.
Sido B, Lasitschka F, Giese T, Gassler N, Funke B, Schröder-Braunstein J, Brunnemer U, Meuer SC, Autschbach F (2008) A prominent role for mucosal cystine/cysteine metabolism in intestinal immunoregulation. Gastroenterology 134(1):179–191PubMedCrossRef
27.
Yan Z, Garg SK, Banerjee R (2010) Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. J Biol Chem 285(53):41525–41532PubMedCentralPubMedCrossRef
28.
Edinger AL, Thompson CB (2002) Antigen-presenting cells control T cell proliferation by regulating amino acid availability. Proc Natl Acad Sci U S A 99(3):1107–1109PubMedCentralPubMedCrossRef
29.
Dröge W, Eck HP, Gmünder H, Mihm S (1991) Dysregulation of plasma amino acid levels in HIV-infection and cancer and its relevance for the immune system. Amino Acids 1(2):193–198PubMedCrossRef
30.
Mihm S, Galter D, Droge W (1995) Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply. FASEB J 9(2):246–252PubMed
31.
Dröge W, Eck HP, Gmunder H, Mihm S (1991) Modulation of lymphocyte functions and immune response by cysteine and cysteine derivatives. Am J Med 91(3C):140S–144SPubMedCrossRef
32.
Grimble RF (2006) The effects of sulfur amino acid intake on immune function in humans. J Nutr 136(6 Suppl):1660S–1665SPubMed
33.
Murphy G, Fan JH, Mark SD, Dawsey SM, Selhub J, Wang J, Taylor PR, Qiao YL, Abnet CC (2011) Prospective study of serum cysteine levels and oesophageal and gastric cancers in China. Gut 60(5):618–623PubMedCentralPubMedCrossRef
34.
Gostner JM, Becker K, Fuchs D, Sucher R (2013) Redox regulation of the immune response. Redox Rep 18(3):88–94PubMedCrossRef
35.
36.
Matsue H, Edelbaum D, Shalhevet D, Mizumoto N, Yang C, Mummert ME et al (2003) Generation and function of reactive oxygen species in dendritic cells during antigen presentation. J Immunol 171(6):3010–3018PubMedCrossRef
37.
Los M, Schenk H, Hexel K, Baeuerle PA, Dröge W, Schulze-Osthoff K (1995) IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase. EMBO J 14(15):3731–3740PubMedCentralPubMed
38.
Miller TW, Wang EA, Gould S, Stein EV, Kaur S, Lim L, Amarnath S, Fowler DH, Roberts DD (2012) Hydrogen sulfide is an endogenous potentiator of T cell activation. J Biol Chem 287(6):4211–4221PubMedCentralPubMedCrossRef
39.
Kontny E, Szczepanska K, Kowalczewski J, Kurowska M, Janicka I, Marcinklewicz J, Maslinski W (2000) The mechanism of taurine chloramine inhibition of cytokine IL-6, IL-8 production by rheumatoid arthritis fibroblast-like synoviocytes. Arthritis Rheum 43(10):2169–2177PubMedCrossRef
40.
Grimble RF (1994) Sulphur amino acids and the metabolic response to cytokines. Adv Exp Med Biol 359:41–49PubMedCrossRef
41.
42.
Grimble RF (1996) Theory and efficacy of antioxidant therapy. Curr Opin Crit Care 2:260–266CrossRef
43.
Chorazy M, Kontny E, Marcinklewicz J, Maslinski W (2002) Taurine chloramine modulates cytokine production by human peripheral blood mononuclear cells. Amino Acids 23(4):407–413PubMedCrossRef
44.
Winder B, Lebilhuber F, Frick B, Laich A, Artner-Dworzak E, Fuchs D (2002) Moderate hyperchromocysteinaemia ad immune activation in Parkinson’s disease. J Neural Transm 109(12):1445–1452CrossRef
45.
Gottfried E, Kreutz M, Mackensen A (2012) Tumor metabolism as modulator of immune response and tumor progression. Semin Cancer Biol 22:335–341PubMedCrossRef
46.
Newsholme P (2001) Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J Nutr 131(9 Suppl):2512–2522
47.
Wilmore DW, Shabert JK (1998) The role of glutamine in immunologic responses. Nutrition 14(4):618–626PubMedCrossRef
48.
Hammami I, Chen J, Bronte V, DeCrescenzo G, Jolicoeur M (2012) L-glutamine is a key parameter in the immunosuppression phenomenon. Biochem Biophys Res Commun 425(4):724–729PubMedCrossRef
49.
Raber P, Ochoa AC, Paulo C (2012) Metabolism of L-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives. Immunol Investig 41(6–7):614–634CrossRef
50.
Barbul A (1990) Arginine and immune function. Nutrition 6(6–7):53–58PubMed
51.
Taheri F, Ochoa JB, Faghiri Z, Culotta K, Park HJ, Lan MS et al (2001) L-Arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta) in Jurkat cells. Clin Cancer Res 7(3 Suppl):958s–965sPubMed
52.
Rodrigez PC, Zen AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC (2002) Regulation of T cell receptor CD3 zeta chain expression by L-arginine. J Biol Chem 277(24):21123–21129CrossRef
53.
Albina JE, Caldwell MD, Henry WL Jr, Mills CD (1989) Regulation of macrophage functions by L-arginine. J Exp Med 169(3):1021–1029PubMedCrossRef
54.
Popovic PJ, Zeh HJ 3rd, Ochoa JB (2007) Arginine and immunity. J Nutr 137(6 Suppl 2):1681S–1686SPubMed
55.
DeSanctis F, Sandri S, Ferrarini G, Pagliarello I, Sartoris S, Ugel S, Marigo I, Molon B, Bronte V (2014) The emerging immunological role of post-translational modifications by reactive nitrogen species in cancer microenvironment. Front Immunol 5:1–16
56.
Terabe M, Swann J, Ambrosino E et al (2005) A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cells is sufficient for down-regulation of tumor immunosurveillance. J Exp Med 202(12):1627–1633PubMedCentralPubMedCrossRef
57.
Takahashi A, Hanson MGV, Norell HR et al (2005) Preferential cell death of CD8+ effector memory (CCR7−CD45RA−) T cells by hudrogen peroxide-induced oxidative stress. J Immunol (Baltimore) 174(10):6080–6087
58.
Schroder AJ, Pavlidis P, Arimura A, Capece D, Rothman PB (2002) Cutting edge: STAT6 serves as a positive and negative regulator of gene expression in IL-4-stimulated B lymphocytes. J Immunol 168(3):996–1000PubMedCrossRef
59.
Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R (2011) Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res 17(22):6985–6991PubMedCrossRef
60.
Mellor AL, Munn DH (2001) Tryptophan catabolism prevents maternal T cells from activating lethal anti-fetal immune responses. J Reprod Immunol 52(1–2):5–13PubMedCrossRef
61.
Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189(9):1363–1372PubMedCentralPubMedCrossRef
62.
Lee GK, Park HJ, Macleod M, Chandler P, Munn DH, Mellor AL (2002) Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology 107(4):452–460PubMedCentralPubMedCrossRef
63.
Weinlich G, Murr C, Richardsen L, Winkler C, Fuchs D (2007) Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients. Dermatology 214(1):8–14PubMedCrossRef
64.
Brandacher G, Perathoner A, Ladurner R, Schneeberger S, Obrist P, Winkler C, Werner ER, Werner-Felmayer G, Weiss HG, Göbel G, Margreiter R, Königsrainer A, Fuchs D, Amberger A (2006) Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res 12(4):1144–1151PubMedCrossRef
65.
Ramanathan A, Wang C, Schreiber SL (2005) Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements. Proc Natl Acad Sci U S A 102(17):5992–5997PubMedCentralPubMedCrossRef
66.
Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR et al (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64(11):3892–3899PubMedCrossRef
67.
Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, Jugold M, Guillemin GJ, Miller CL, Lutz C, Radlwimmer B, Lehmann I, von Deimling A, Wick W, Platten M (2011) An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478(7368):197–203PubMedCrossRef
68.
Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Frédérick R, De Plaen E, Uyttenhove C, Wouters J, Masereel B, Van den Eynde BJ (2012) Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A 109(7):2497–2502PubMedCentralPubMedCrossRef
69.
Platten M, Wick W, Van den Eynde BJ (2012) Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res 72(21):5435–5440PubMedCrossRef
70.
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillence to tumor escape. Nat Immunol 3(11):991–998PubMedCrossRef
71.
Mizoguchi H, O’Shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258(5089):1795–1798PubMedCrossRef
72.
Lee J-I, Dominy JE Jr, Sikalidis AK, Hirschberger LL, Wang W, Stipanuk MH (2008) HepG2/C3A cells respond to cysteine-deprivation by induction of the amino acid deprivation/integrated stress response pathway. Physiol Genomics 33(2):218–229PubMedCrossRef
73.
Sikalidis AK, Mazor KM, Kang M, Liu H, Stipanuk MH (2013) Total 4EBP1 is elevated in liver of rats in response to low sulfur amino acid intake. J Amino Acids 2013:864757PubMedCentralPubMedCrossRef
74.
Sikalidis AK (2013) Cellular and animal indispensable amino acid limitation responses and health promotion. Can the two be linked? A critical review. Int J Food Sci Nutr 64(3):300–311PubMedCrossRef
75.
Maciolek JA, Pasternak JA, Wilson HL (2014) Metabolism of activated T lymphocytes. Curr Opin Immunol 27:60–74PubMedCrossRef
76.
Baracos VE, Mackenzie ML (2006) Investigations of branched-chain amino acids and their metabolites in animal models of cancer. J Nutr 136(1 Suppl):237S–242SPubMed
Metadaten
Titel
Amino Acids and Immune Response: A Role for Cysteine, Glutamine, Phenylalanine, Tryptophan and Arginine in T-cell Function and Cancer?
verfasst von
Angelos K. Sikalidis
Publikationsdatum
01.01.2015
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 1/2015
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-014-9860-0

Weitere Artikel der Ausgabe 1/2015

Pathology & Oncology Research 1/2015 Zur Ausgabe

Research

Pathologic Assessment of Response to Chemotherapy in Colorectal Cancer Liver Metastases after Hepatic Resection: Which Method to Use?

Research

Metallothionein 3 Expression in Normal Skin and Malignant Skin Lesions

Research

Expression of Human Papillomavirus is Correlated with Ki-67 and COX-2 Expressions in Keratocystic Odontogenic Tumor

Research

Elevated Proinflammatory Cytokine IL-17A in the Adjacent Tissues Along the Adenoma-Carcinoma Sequence

Review

Meta-Analysis of Oncological Outcome After Abdominoperineal Resection or Low Anterior Resection for Lower Rectal Cancer

Research

Different Methods of Pretreatment Ki-67 Labeling Index Evaluation in Core Biopsies of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Their Relation to Response to Therapy

Neu im Fachgebiet Onkologie

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

23.05.2024 Leitsymptome in der Hausarztpraxis Nachrichten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise