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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. 
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Immunologic Research

01.05.2024 | REVIEW

The immunosuppressive landscape in tumor microenvironment

verfasst von: Wuyi Liu, Huyue Zhou, Wenjing Lai, Changpeng Hu, Rufu Xu, Peng Gu, Menglin Luo, Rong Zhang, Guobing Li

Erschienen in: Immunologic Research

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Abstract

Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.
Literatur
1.
2.
Schreiber RD, et al. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.PubMedCrossRef
3.
Kakavand H, et al. Targeted therapies and immune checkpoint inhibitors in the treatment of metastatic melanoma patients: a guide and update for pathologists. Pathology. 2016;48(2):194–202.PubMedCrossRef
4.
5.
Herbst RS, et al. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446–54.PubMedCrossRef
6.
Emens LA et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer. J Immunother Cancer. 2021;9(8).
7.
Topalian SL et al. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science. 2020;367(6477).
8.
9.
Alsaab HO, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.PubMedPubMedCentralCrossRef
10.
11.
12.
Yuan Y, et al. Recent advancements in the mechanisms underlying resistance to PD-1/PD-L1 Blockade Immunotherapy. Cancers (Basel). 2021;13(4):663.PubMedCrossRef
13.
Hargadon KM, et al. Immune checkpoint blockade therapy for cancer: an overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol. 2018;62:29–39.PubMedCrossRef
14.
Bagchi S, et al. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol. 2021;16:223–49.PubMedCrossRef
15.
16.
Wang J, et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell. 2019;176(1–2):334-47 e12.PubMedCrossRef
17.
Maruhashi T, et al. Binding of LAG-3 to stable peptide-MHC class II limits T cell function and suppresses autoimmunity and anti-cancer immunity. Immunity. 2022;55(5):912-24 e8.PubMedCrossRef
18.
Hirayasu K, et al. Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations. J Hum Genet. 2015;60(11):703–8.PubMedCrossRef
19.
Stahl M, et al. Immune checkpoint inhibitors in acute myeloid leukemia: novel combinations and therapeutic targets. Curr Oncol Rep. 2019;21(4):37.PubMedCrossRef
20.
21.
Sharma N, et al. LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy. J Exp Med. 2021;218(7):e20201811.
22.
Inui M, et al. Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE. Int Immunol. 2016;28(12):597–604.PubMedCrossRef
23.
Sugahara-Tobinai A, et al. Augmented ILT3/LILRB4 expression of peripheral blood antibody secreting cells in the acute phase of Kawasaki disease. Pediatr Infect Dis J. 2019;38(4):431–8.PubMedCrossRef
24.
Thies A, et al. CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease. J Clin Oncol. 2002;20(10):2530–6.PubMedCrossRef
25.
Huang YH, et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2015;517(7534):386-U566.PubMedCrossRef
26.
27.
Markel G, et al. CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. J Immunol. 2002;168(6):2803–10.PubMedCrossRef
28.
29.
Hirota T, et al. Transcriptional activation of the mouse Necl-5/Tage4/PVR/CD155 gene by fibroblast growth factor or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway. Oncogene. 2005;24(13):2229–35.PubMedCrossRef
30.
Casado JG, et al. Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines. Cancer Immunol Immunother. 2009;58(9):1517–26.PubMedPubMedCentralCrossRef
31.
Ozmadenci D, et al. Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis. Proc Natl Acad Sci USA. 2022;119(17): e2117065119.PubMedPubMedCentralCrossRef
32.
Nishiwada S, et al. Clinical significance of CD155 expression in human pancreatic cancer. Anticancer Res. 2015;35(4):2287–97.PubMed
33.
Nakai R, et al. Overexpression of Necl-5 correlates with unfavorable prognosis in patients with lung adenocarcinoma. Cancer Sci. 2010;101(5):1326–30.PubMedCrossRef
34.
35.
Curley J, et al. Looking past PD-L1: expression of immune checkpoint TIM-3 and its ligand galectin-9 in cervical and vulvar squamous neoplasia. Mod Pathol. 2020;33(6):1182–92.PubMedCrossRef
36.
37.
38.
Su M, et al. ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses. Cell Mol Immunol. 2021;18(8):1920–33.PubMedCrossRef
39.
Xiang J, et al. Disruption of SIRT7 increases the efficacy of checkpoint inhibitor via mef2d regulation of programmed cell death 1 ligand 1 in hepatocellular carcinoma cells. Gastroenterology. 2020;158(3):664-78 e24.PubMedCrossRef
40.
41.
Rizvi NA, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.PubMedPubMedCentralCrossRef
42.
Yarchoan M, et al. PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI Insight. 2019;4(6):e126908.
43.
44.
45.
Schrock AB, et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann Oncol. 2019;30(7):1096–103.PubMedCrossRef
46.
Mandal R, et al. Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response. Science. 2019;364(6439):485–91.PubMedPubMedCentralCrossRef
47.
McGranahan N, et al. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168(4):613–28.PubMedCrossRef
48.
McGranahan N, et al. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell. 2015;27(1):15–26.PubMedCrossRef
49.
Kreso A, et al. Evolution of the cancer stem cell model. Cell Stem Cell. 2014;14(3):275–91.PubMedCrossRef
50.
51.
Anagnostou V, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017;7(3):264–76.PubMedCrossRef
52.
53.
Brown SD, et al. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res. 2014;24(5):743–50.PubMedPubMedCentralCrossRef
54.
Lauss M, et al. Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma. Nat Commun. 2017;8(1):1738.PubMedPubMedCentralCrossRef
55.
Campoli M, et al. HLA class I antigen loss, tumor immune escape and immune selection. Vaccine. 2002;20(Suppl 4):A40–5.PubMedCrossRef
56.
57.
Marincola FM, et al. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol. 2000;74:181–273.PubMed
58.
Pereira C, et al. Genomic profiling of patient-derived xenografts for lung cancer identifies B2M inactivation impairing immunorecognition. Clin Cancer Res. 2017;23(12):3203–13.PubMedCrossRef
59.
Roh W, et al. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci Transl Med. 2017;9(379):eaah3560.
60.
61.
62.
63.
Huang L, et al. The RNA-binding protein MEX3B mediates resistance to cancer immunotherapy by downregulating HLA-A expression. Clin Cancer Res. 2018;24(14):3366–76.PubMedPubMedCentralCrossRef
64.
65.
Chew GL, et al. DUX4 suppresses MHC class I to promote cancer immune evasion and resistance to checkpoint blockade. Dev Cell. 2019;50(5):658-71 e7.PubMedPubMedCentralCrossRef
66.
Hurwitz AA, et al. Costimulatory wars: the tumor menace. Curr Opin Immunol. 2000;12(5):589–96.PubMedCrossRef
67.
68.
Banchereau J, et al. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.PubMedCrossRef
69.
Sanchez-Paulete AR, et al. Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy. Ann Oncol. 2017;28(suppl_12):xii74.PubMedCrossRef
70.
Bandola-Simon J, et al. Dysfunction of antigen processing and presentation by dendritic cells in cancer. Mol Immunol. 2019;113:31–7.PubMedCrossRef
71.
72.
Dammeijer F, et al. Rationally combining immunotherapies to improve efficacy of immune checkpoint blockade in solid tumors. Cytokine Growth Factor Rev. 2017;36:5–15.PubMedCrossRef
73.
Kadam P, et al. PD-1 Immune checkpoint blockade promotes therapeutic cancer vaccine to eradicate lung cancer. Vaccines (Basel). 2020;8(2):317.PubMedCrossRef
74.
Antonios JP, et al. PD-1 blockade enhances the vaccination-induced immune response in glioma. JCI Insight. 2016;1(10):e87059.
75.
76.
Schietinger A, et al. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 2014;35(2):51–60.PubMedCrossRef
77.
78.
79.
Hosseini A, et al. CTLA-4: From mechanism to autoimmune therapy. Int Immunopharmacol. 2020;80: 106221.PubMedCrossRef
80.
Anderson AC, et al. Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44(5):989–1004.PubMedPubMedCentralCrossRef
81.
Monney L, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415(6871):536–41.PubMedCrossRef
82.
Anderson AC. Tim-3, a negative regulator of anti-tumor immunity. Curr Opin Immunol. 2012;24(2):213–6.PubMedCrossRef
83.
Zhang Y, et al. TIM-3 is a potential prognostic marker for patients with solid tumors: a systematic review and meta-analysis. Oncotarget. 2017;8(19):31705–13.PubMedPubMedCentralCrossRef
84.
Yu X, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48–57.PubMedCrossRef
85.
Stanietsky N, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci USA. 2009;106(42):17858–63.PubMedPubMedCentralCrossRef
86.
87.
Lozano E, et al. The TIGIT/CD226 axis regulates human T cell function. J Immunol. 2012;188(8):3869–75.PubMedCrossRef
88.
Napoleon JV, et al. Design, synthesis, and targeted delivery of an immune stimulant that selectively reactivates exhausted CAR T cells. Angew Chem Int Ed Engl. 2022;61(15): e202113341.PubMedCrossRef
89.
90.
Alissafi T, et al. Balancing cancer immunotherapy and immune-related adverse events: the emerging role of regulatory T cells. J Autoimmun. 2019;104: 102310.PubMedCrossRef
91.
Sato E, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102(51):18538–43.PubMedPubMedCentralCrossRef
92.
93.
Fisher SA, et al. Transient Treg depletion enhances therapeutic anti-cancer vaccination. Immun Inflamm Dis. 2017;5(1):16–28.PubMedCrossRef
94.
Angelova M, et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol. 2015;16:64.PubMedPubMedCentralCrossRef
95.
96.
Li T, et al. Targeting MDSC for immune-checkpoint blockade in cancer immunotherapy: current progress and new prospects. Clin Med Insights Oncol. 2021;15:11795549211035540.PubMedPubMedCentralCrossRef
97.
98.
Ugel S, et al. Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest. 2015;125(9):3365–76.PubMedPubMedCentralCrossRef
99.
100.
Novitskiy SV, et al. TGF-beta receptor II loss promotes mammary carcinoma progression by Th17 dependent mechanisms. Cancer Discov. 2011;1(5):430–41.PubMedPubMedCentralCrossRef
101.
Messmer MN, et al. Tumor-induced myeloid dysfunction and its implications for cancer immunotherapy. Cancer Immunol Immunother. 2015;64(1):1–13.PubMedCrossRef
102.
Solito S, et al. Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci. 2014;1319:47–65.PubMedCrossRef
103.
Meyer C, et al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother. 2014;63(3):247–57.PubMedCrossRef
104.
Tarhini AA, et al. Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. PLoS ONE. 2014;9(2): e87705.PubMedPubMedCentralCrossRef
105.
Zhu Y, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014;74(18):5057–69.PubMedPubMedCentralCrossRef
106.
Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582–98.PubMedCrossRef
107.
Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;10(10):712–23.PubMedCrossRef
108.
Joyce JA, et al. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348(6230):74–80.PubMedCrossRef
109.
Cazet AS, et al. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat Commun. 2018;9(1):2897.PubMedPubMedCentralCrossRef
110.
Kakarla S, et al. Cancer-associated fibroblasts as targets for immunotherapy. Immunotherapy. 2012;4(11):1129–38.PubMedCrossRef
111.
Al-Bzour NN, et al. Cancer-associated fibroblasts in gastrointestinal cancers: unveiling their dynamic roles in the tumor microenvironment. Int J Mol Sci. 2023;24(22):16505.PubMedPubMedCentralCrossRef
112.
113.
Gong X, et al. Microvesicle-inspired oxygen-delivering nanosystem potentiates radiotherapy-mediated modulation of tumor stroma and antitumor immunity. Biomaterials. 2022;290: 121855.PubMedCrossRef
114.
Liu Y, et al. FAP-targeted CAR-T suppresses MDSCs recruitment to improve the antitumor efficacy of claudin18.2-targeted CAR-T against pancreatic cancer. J Transl Med. 2023;21(1):255.PubMedPubMedCentralCrossRef
115.
Franco-Barraza J, et al. Matrix-regulated integrin alpha(v)beta(5) maintains alpha(5)beta(1)-dependent desmoplastic traits prognostic of neoplastic recurrence. Elife. 2017;6:e20600.
116.
Tauriello DVF, et al. Overcoming TGFbeta-mediated immune evasion in cancer. Nat Rev Cancer. 2022;22(1):25–44.PubMedCrossRef
117.
Hu J, et al. Cell membrane-anchored and tumor-targeted IL-12 T-cell therapy destroys cancer-associated fibroblasts and disrupts extracellular matrix in heterogenous osteosarcoma xenograft models. J Immunother Cancer. 2024;12(1):e006991.
118.
119.
120.
Zheng X, et al. Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy. Oncotarget. 2017;8(29):48436–52.PubMedPubMedCentralCrossRef
121.
Movahedi K, et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 2010;70(14):5728–39.PubMedCrossRef
122.
123.
Zhu Y, et al. Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade. Gut. 2019;68(9):1653–66.PubMedCrossRef
124.
Ramesh A, et al. CSF1R- and SHP2-inhibitor-loaded nanoparticles enhance cytotoxic activity and phagocytosis in tumor-associated macrophages. Adv Mater. 2019;31(51): e1904364.PubMedCrossRef
125.
126.
Shahbaz S, et al. CD71+VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-beta. PLoS Biol. 2018;16(12): e2006649.PubMedPubMedCentralCrossRef
127.
128.
Chen J, et al. Intratumoral CD45(+)CD71(+) erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma. Cancer Lett. 2021;499:85–98.PubMedCrossRef
129.
Long H, et al. Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy. Cancer Cell. 2022;40(6):674-93 e7.PubMedCrossRef
130.
Wellenstein MD, et al. Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity. 2018;48(3):399–416.PubMedCrossRef
131.
132.
Lu Y, et al. JAK/STAT and PI3K/AKT pathways form a mutual transactivation loop and afford resistance to oxidative stress-induced apoptosis in cardiomyocytes. Cell Physiol Biochem. 2008;21(4):305–14.PubMedCrossRef
133.
Darnell JE Jr, et al. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994;264(5164):1415–21.PubMedCrossRef
134.
135.
Owen KL, et al. JAK-STAT signaling: a double-edged sword of immune regulation and cancer progression. Cancers (Basel). 2019;11(12):2002.PubMedCrossRef
136.
137.
Zhang X, et al. Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19. Int Immunopharmacol. 2020;86: 106749.PubMedPubMedCentralCrossRef
138.
Li S, et al. Discovery of oral-available resveratrol-caffeic acid based hybrids inhibiting acetylated and phosphorylated STAT3 protein. Eur J Med Chem. 2016;124:1006–18.PubMedCrossRef
139.
Xu J, et al. Flavopereirine suppresses the progression of human oral cancer by inhibiting the JAK-STAT signaling pathway via targeting LASP1. Drug Des Devel Ther. 2021;15:1705–16.PubMedPubMedCentralCrossRef
140.
141.
Dao KT, et al. Efficacy of ruxolitinib in patients with chronic neutrophilic leukemia and atypical chronic myeloid leukemia. J Clin Oncol. 2020;38(10):1006–18.PubMedCrossRef
142.
143.
Vitale M, et al. NK-active cytokines IL-2, IL-12, and IL-15 selectively modulate specific protein kinase C (PKC) isoforms in primary human NK cells. Anat Rec. 2002;266(2):87–92.PubMedCrossRef
144.
Gotthardt D, et al. STATs in NK-cells: the good, the bad, and the ugly. Front Immunol. 2016;7:694.PubMed
145.
146.
Wu L, et al. Signal transducer and activator of transcription 3 (Stat3C) promotes myeloid-derived suppressor cell expansion and immune suppression during lung tumorigenesis. Am J Pathol. 2011;179(4):2131–41.PubMedPubMedCentralCrossRef
147.
Fu C, et al. beta-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10. Proc Natl Acad Sci USA. 2015;112(9):2823–8.PubMedPubMedCentralCrossRef
148.
149.
Dhillon AS, et al. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–90.PubMedCrossRef
150.
de Sauvage MA, et al. The ERK inhibitor LY3214996 augments anti-PD-1 immunotherapy in preclinical mouse models of BRAFV600E melanoma brain metastasis. Neuro Oncol. 2023:noad248.
151.
Sumimoto H, et al. The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells. J Exp Med. 2006;203(7):1651–6.PubMedPubMedCentralCrossRef
152.
Liu C, et al. BRAF inhibition increases tumor infiltration by T cells and enhances the antitumor activity of adoptive immunotherapy in mice. Clin Cancer Res. 2013;19(2):393–403.PubMedCrossRef
153.
154.
155.
Jiang X, et al. The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res. 2013;19(3):598–609.PubMedCrossRef
156.
Feng D, et al. BRAF(V600E)-induced, tumor intrinsic PD-L1 can regulate chemotherapy-induced apoptosis in human colon cancer cells and in tumor xenografts. Oncogene. 2019;38(41):6752–66.PubMedPubMedCentralCrossRef
157.
D’Souza WN, et al. The Erk2 MAPK regulates CD8 T cell proliferation and survival. J Immunol. 2008;181(11):7617–29.PubMedCrossRef
158.
159.
Ebert PJR, et al. MAP kinase inhibition promotes t cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity. 2016;44(3):609–21.PubMedCrossRef
160.
Kosnopfel C, et al. Inhibition of p90 ribosomal S6 kinases disrupts melanoma cell growth and immune evasion. J Exp Clin Cancer Res. 2023;42(1):175.PubMedPubMedCentralCrossRef
161.
Biswas SK. Metabolic reprogramming of immune cells in cancer progression. Immunity. 2015;43(3):435–49.PubMedCrossRef
162.
163.
164.
Almeida L, et al. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016;28(5):514–24.PubMedCrossRef
165.
Liu X, et al. Tumor microenvironment metabolites directing T cell differentiation and function. Trends Immunol. 2022;43(2):132–47.PubMedCrossRef
166.
167.
Zurier RB, et al. Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 1999;60(5–6):371–5.PubMedCrossRef
168.
Lima TM, et al. Ranking the toxicity of fatty acids on Jurkat and Raji cells by flow cytometric analysis. Toxicol In Vitro. 2002;16(6):741–7.PubMedCrossRef
169.
Haas R, et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T Cell migration and effector functions. PLoS Biol. 2015;13(7): e1002202.PubMedPubMedCentralCrossRef
170.
171.
172.
Martinvalet D. The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses. Cell Death Dis. 2018;9(3):336.PubMedPubMedCentralCrossRef
173.
Yang M, et al. Serine and one-carbon metabolism in cancer. Nat Rev Cancer. 2016;16(10):650–62.PubMedCrossRef
174.
175.
Kawalekar OU, et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity. 2016;44(2):380–90.PubMedCrossRef
176.
van Bruggen JAC, et al. Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8(+) T cells and impede CAR T-cell efficacy. Blood. 2019;134(1):44–58.PubMedPubMedCentralCrossRef
177.
178.
Fletcher M, et al. l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res. 2015;75(2):275–83.PubMedCrossRef
179.
Rodriguez PC, et al. L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol. 2003;171(3):1232–9.PubMedCrossRef
180.
Lamas B, et al. Altered functions of natural killer cells in response to L-arginine availability. Cell Immunol. 2012;280(2):182–90.PubMedCrossRef
181.
Yu J, et al. Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol. 2013;190(7):3783–97.PubMedCrossRef
182.
183.
184.
185.
Qin R, et al. Tryptophan potentiates CD8(+) T cells against cancer cells by TRIP12 tryptophanylation and surface PD-1 downregulation. J Immunother Cancer. 2021;9(7):e002840.
186.
Liu Y, et al. IL-2 regulates tumor-reactive CD8(+) T cell exhaustion by activating the aryl hydrocarbon receptor. Nat Immunol. 2021;22(3):358–69.PubMedCrossRef
187.
Opitz CA, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;478(7368):197–203.PubMedCrossRef
188.
Frumento G, et al. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med. 2002;196(4):459–68.PubMedPubMedCentralCrossRef
189.
Della Chiesa M, et al. The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood. 2006;108(13):4118–25.PubMedCrossRef
190.
Zhao F, et al. Paracrine Wnt5a-beta-catenin signaling triggers a metabolic program that drives dendritic cell tolerization. Immunity. 2018;48(1):147-60 e7.PubMedPubMedCentralCrossRef
191.
Nguyen NT, et al. Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci USA. 2010;107(46):19961–6.PubMedPubMedCentralCrossRef
192.
Rodriguez PC, et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69(4):1553–60.PubMedPubMedCentralCrossRef
193.
Horig H, et al. Exogenous glutamine requirement is confined to late events of T cell activation. J Cell Biochem. 1993;53(4):343–51.PubMedCrossRef
194.
Carr EL, et al. Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J Immunol. 2010;185(2):1037–44.PubMedCrossRef
195.
Klysz D, et al. Glutamine-dependent alpha-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci Signal. 2015;8(396):ra97.PubMedCrossRef
196.
Metzler B, et al. Restricting glutamine or glutamine-dependent purine and pyrimidine syntheses promotes human T cells with high FOXP3 expression and regulatory properties. J Immunol. 2016;196(9):3618–30.PubMedCrossRef
197.
Ma EH, et al. Serine is an essential metabolite for effector T cell expansion. Cell Metab. 2017;25(2):345–57.PubMedCrossRef
198.
Siska PJ, et al. Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes. J Immunol Methods. 2016;438:51–8.PubMedPubMedCentralCrossRef
199.
Gmunder H, et al. Low membrane transport activity for cystine in resting and mitogenically stimulated human lymphocyte preparations and human T cell clones. Eur J Biochem. 1991;201(1):113–7.PubMedCrossRef
200.
Srivastava MK, et al. Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 2010;70(1):68–77.PubMedCrossRef
201.
Wu J, et al. Asparagine enhances LCK signalling to potentiate CD8(+) T-cell activation and anti-tumour responses. Nat Cell Biol. 2021;23(1):75–86.PubMedCrossRef
202.
203.
Franek F, et al. Protection of B lymphocyte hybridoma against starvation-induced apoptosis: survival-signal role of some amino acids. Immunol Lett. 1996;52(2–3):139–44.PubMedCrossRef
204.
Hayashi K, et al. LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells. J Immunol. 2013;191(8):4080–5.PubMedCrossRef
205.
206.
Sinclair LV, et al. Antigen receptor control of methionine metabolism in T cells. Elife. 2019;8:e44210.
207.
Hale LL, et al. Isoleucine needs of thirty- to forty-day-old female chickens: immunity. Poult Sci. 2004;83(12):1979–85.PubMedCrossRef
208.
209.
Assmann N, et al. Srebp-controlled glucose metabolism is essential for NK cell functional responses. Nat Immunol. 2017;18(11):1197–206.PubMedCrossRef
210.
Brand A, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 2016;24(5):657–71.PubMedCrossRef
211.
Husain Z, et al. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol. 2013;191(3):1486–95.PubMedCrossRef
212.
213.
Calder PC. Functional roles of fatty acids and their effects on human health. JPEN J Parenter Enteral Nutr. 2015;39(1 Suppl):18S-32S.PubMed
214.
215.
Ma X, et al. CD36-mediated ferroptosis dampens intratumoral CD8(+) T cell effector function and impairs their antitumor ability. Cell Metab. 2021;33(5):1001-12 e5.PubMedPubMedCentralCrossRef
216.
217.
218.
Everts B, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKvarepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol. 2014;15(4):323–32.PubMedPubMedCentralCrossRef
219.
Cubillos-Ruiz JR, et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell. 2015;161(7):1527–38.PubMedPubMedCentralCrossRef
220.
Bose D, et al. Inhibition of TGF-beta induced lipid droplets switches M2 macrophages to M1 phenotype. Toxicol In Vitro. 2019;58:207–14.PubMedCrossRef
221.
222.
Metadaten
Titel
The immunosuppressive landscape in tumor microenvironment
verfasst von
Wuyi Liu
Huyue Zhou
Wenjing Lai
Changpeng Hu
Rufu Xu
Peng Gu
Menglin Luo
Rong Zhang
Guobing Li
Publikationsdatum
01.05.2024
Verlag
Springer US
Erschienen in
Immunologic Research
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-024-09483-8

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