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  4. Vol 1, Issue 2, 2023

Tumor Cell Ferroptosis as a "Game Changer" in the Tumor Immune Microenvironment

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DOI: 10.23977/medbm.2023.010206 | Downloads: 15 | Views: 427

Author(s)

Zixun Wang 1, Daowei Li 1

Affiliation(s)

1 Jilin Provincial Key Laboratory of Oral Biomedical Engineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China

Corresponding Author

Daowei Li

ABSTRACT

The tumor immune microenvironment (TIME) is a critical determinant of tumor progression, response to treatment, and overall patient prognosis. An intricate network of cellular and molecular interactions within the TIME regulates immune responses against tumors. Recently, ferroptosis, a novel form of regulated cell death characterized by an overload of intracellular iron and lipid peroxidation, has emerged as a significant player in the TIME. Tumor cells are naturally susceptible to ferroptosis, and tumor cells undergoing ferroptosis secrete damage-associated molecular patterns, lipid metabolites, ferroptosis-related proteins, as well as "find me" and "eat me" signals, which interacts with immune cells in the surrounding tumor microenvironment, thus affecting the growth and development of cancer. This review article delves into the role of ferroptosis in modulating the tumor immune landscape, highlighting its potential as a "game changer" in cancer therapy. Ferroptosis in tumor cells can alter the TIME by modulating immune cell infiltration and activation, affecting cytokine and chemokine profiles, and influencing antigen presentation. We dissect the latest findings on the mechanistic interplay between ferroptosis and immune cells, including macrophages, dendritic cells, and T cells. Furthermore, we explore how targeting ferroptosis pathways may pave the way for new therapeutic strategies, particularly in combination with current immunotherapies. This comprehensive review provides insights for researchers and clinicians alike, aiming to harness the potential of ferroptosis to transform the therapeutic landscape of oncology.

KEYWORDS

Ferroptosis, cell death, immunity, tumor microenvironment, damage-associated molecular pattern, lipid peroxidation, iron metabolism

CITE THIS PAPER

Zixun Wang, Daowei Li, Tumor Cell Ferroptosis as a "Game Changer" in the Tumor Immune Microenvironment. MEDS Basic Medicine (2023) Vol. 1: 32-39. DOI: http://dx.doi.org/10.23977/medbm.2023.010206.

REFERENCES

[1] Costa A, Scholer-Dahirel A, Mechta-Grigoriou F. The role of reactive oxygen species and metabolism on cancer cells and their microenvironment[J]. Semin Cancer Biol, 2014, 25: 23-32.
[2] Warburg O H, Negelein E, Posener K. Versuche an Überlebendem Carcinomgewebe[J]. Klinische Wochenschrift, 1923, 3: 1062-1064.
[3] CF Cori, GT Cori. The Carbohydrate Metabolism of Tumors: Ii. Changes in the Sugar, Lactic Acid, and Co2-Combining Power of Blood Passing through a Tumor[J]. Journal of Biological Chemistry, 1925, 65(2): 397-405.
[4] Yu L, Chen X, Wang L, et al. The sweet trap in tumors: aerobic glycolysis and potential targets for therapy[J]. Oncotarget, 2016, 7(25): 38908-38926.
[5] Gwangwa M V, Joubert A M, Visagie M H. Crosstalk between the Warburg effect, redox regulation and autophagy induction in tumourigenesis[J]. Cell Mol Biol Lett, 2018, 23: 20.
[6] Hanahan D, Weinberg R A. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-674.
[7] Viswanathan V S, Ryan M J, Dhruv H D, et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway[J]. Nature, 2017, 547(7664): 453-457.
[8] Verma N, Vinik Y, Saroha A, et al. Synthetic lethal combination targeting BET uncovered intrinsic susceptibility of TNBC to ferroptosis[J]. Sci Adv, 2020, 6(34).
[9] Cassim S, Pouyssegur J. Tumor Microenvironment: A Metabolic Player that Shapes the Immune Response[J]. Int J Mol Sci, 2019, 21(1).
[10] Li J, Yuan S, Norgard R J, et al. Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer[J]. Cancer Discov, 2021, 11(3): 736-753.
[11] Green D R, Ferguson T, Zitvogel L, et al. Immunogenic and tolerogenic cell death[J]. Nat Rev Immunol, 2009, 9(5): 353-363.
[12] Kepp O, Marabelle A, Zitvogel L, et al. Oncolysis without viruses—inducing systemic anticancer immune responses with local therapies[J]. Nat Rev Clin Oncol, 2020, 17(1): 49-64.
[13] Galluzzi L, Vitale I, Warren S, et al. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death[J]. J Immunother Cancer, 2020, 8(1).
[14] Kepp O, Zitvogel L, Kroemer G. Clinical evidence that immunogenic cell death sensitizes to PD-1/PD-L1 blockade[J]. Oncoimmunology, 2019, 8(10): e1637188.
[15] Efimova I, Catanzaro E, Van Der Meeren L, et al. Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity[J]. J Immunother Cancer, 2020, 8(2).
[16] Sims G P, Rowe D C, Rietdijk S T, et al. HMGB1 and RAGE in inflammation and cancer[J]. Annu Rev Immunol, 2010, 28: 367-388.
[17] Wen Q, Liu J, Kang R, et al. The release and activity of HMGB1 in ferroptosis[J]. Biochem Biophys Res Commun, 2019, 510(2): 278-283.
[18] Demuynck R, Efimova I, Naessens F, et al. Immunogenic ferroptosis and where to find it?[J]. J Immunother Cancer, 2021, 9(12).
[19] Friedmann Angeli J P, Krysko D V, Conrad M. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion[J]. Nat Rev Cancer, 2019, 19(7): 405-414.
[20] Rickard J A, O'donnell J A, Evans J M, et al. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis[J]. Cell, 2014, 157(5): 1175-1188.
[21] Martin-Sanchez D, Ruiz-Andres O, Poveda J, et al. Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid-Induced AKI[J]. J Am Soc Nephrol, 2017, 28(1): 218-229.
[22] Blees A, Januliene D, Hofmann T, et al. Structure of the human MHC-I peptide-loading complex[J]. Nature, 2017, 551(7681): 525-528.
[23] Yu B, Choi B, Li W, et al. Magnetic field boosted ferroptosis-like cell death and responsive MRI using hybrid vesicles for cancer immunotherapy[J]. Nat Commun, 2020, 11(1): 3637.
[24] Liang C, Zhang X, Yang M, et al. Recent Progress in Ferroptosis Inducers for Cancer Therapy[J]. Adv Mater, 2019, 31(51): e1904197.
[25] Wiernicki B, Maschalidi S, Pinney J, et al. Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity[J]. Nat Commun, 2022, 13(1): 3676.
[26] Seeds M, Bass D. Regulation and metabolism of arachidonic acid[J]. Clinical Reviews in Allergy & Immunology, 2007, 17(2): 5-26.
[27] Friedmann Angeli J P, Schneider M, Proneth B, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice[J]. Nat Cell Biol, 2014, 16(12): 1180-1191.
[28] Li C, Deng X, Zhang W, et al. Novel Allosteric Activators for Ferroptosis Regulator Glutathione Peroxidase 4[J]. J Med Chem, 2019, 62(1): 266-275.
[29] Morgan A H, Dioszeghy V, Maskrey B H, et al. Phosphatidylethanolamine-esterified eicosanoids in the mouse: tissue localization and inflammation-dependent formation in Th-2 disease[J]. J Biol Chem, 2009, 284(32): 21185-21191.
[30] Kagan V E, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis[J]. Nat Chem Biol, 2017, 13(1): 81-90.
[31] D'herde K, Krysko D V. Ferroptosis: Oxidized PEs trigger death[J]. Nat Chem Biol, 2017, 13(1): 4-5.
[32] Lauber K, Bohn E, Kröber S M, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal[J]. Cell, 2003, 113(6): 717-730.
[33] Rothe T, Gruber F, Uderhardt S, et al. 12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function[J]. J Clin Invest, 2015, 125(5): 1944-1954.
[34] Dai E, Han L, Liu J, et al. Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein[J]. Autophagy, 2020, 16(11): 2069-2083.
[35] Dai E, Han L, Liu J, et al. Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway[J]. Nat Commun, 2020, 11(1): 6339.
[36] Luis G, Godfroid A, Nishiumi S, et al. Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence[J]. Redox Biol, 2021, 43: 102006.
[37] Veglia F, Tyurin V A, Blasi M, et al. Fatty acid transport protein 2 reprograms neutrophils in cancer[J]. Nature, 2019, 569(7754): 73-78.
[38] Yang W S, Sriramaratnam R, Welsch M E, et al. Regulation of ferroptotic cancer cell death by GPX4[J]. Cell, 2014, 156(1-2): 317-331.
[39] Kalinski P. Regulation of immune responses by prostaglandin E2[J]. J Immunol, 2012, 188(1): 21-28.
[40] Zelenay S, Van Der Veen A G, Böttcher J P, et al. Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity[J]. Cell, 2015, 162(6): 1257-1270.
[41] Böttcher J P, Bonavita E, Chakravarty P, et al. NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control[J]. Cell, 2018, 172(5): 1022-1037.e1014.
[42] Wang D, Dubois R N. Immunosuppression associated with chronic inflammation in the tumor microenvironment [J]. Carcinogenesis, 2015, 36(10): 1085-1093.
[43] Kurtova A V, Xiao J, Mo Q, et al. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance[J]. Nature, 2015, 517(7533): 209-213.
[44] Uderhardt S, Herrmann M, Oskolkova O V, et al. 12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance[J]. Immunity, 2012, 36(5): 834-846.
[45] Blüml S, Kirchberger S, Bochkov V N, et al. Oxidized phospholipids negatively regulate dendritic cell maturation induced by TLRs and CD40[J]. J Immunol, 2005, 175(1): 501-508.
[46] Elliott M R, Ravichandran K S. The Dynamics of Apoptotic Cell Clearance[J]. Dev Cell, 2016, 38(2): 147-160.
[47] Klöditz K, Fadeel B. Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death[J]. Cell Death Discov, 2019, 5: 65.
[48] Luo X, Gong H B, Gao H Y, et al. Oxygenated phosphatidylethanolamine navigates phagocytosis of ferroptotic cells by interacting with TLR2[J]. Cell Death Differ, 2021, 28(6): 1971-1989.

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