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image of Lipopolysaccharide-induced M1-type Macrophages Enhance T Cell Activity and Promote the Apoptosis of Hepatocellular Carcinoma Cells

Abstract

Introduction

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. M1 macrophages exhibit dual roles in the tumor microenvironment (TME), but the specific mechanisms underlying their involvement in HCC remain unclear.

Methods

M1-polarized macrophages were differentiated from THP-1 monocytes employing Phorbol 12-Myristate 13-Acetate (PMA) and lipopolysaccharide (LPS). Then, macrophage activity was determined based on Mean Fluorescence Intensity (MFI), and their metabolic capacity was assessed according to extracellular acidification rate (ECAR) and Oxygen Consumption Rate (OCR). Quantitative Real-Time PCR (qRT-PCR) was performed to assess the expression of polarization-related genes.

Results

The results showed that LPS at a concentration higher than 10 ng/mL significantly affected the viability of macrophages differentiated from THP-1 monocytes but promoted the MFI of CD86. At the same time, LPS treatment notably enhanced the M1 polarization of macrophages, as evidenced by the upregulated expression of markers related to the M1 phenotype. Moreover, the mitochondrial oxidative metabolism of M1 macrophages shifted toward aerobic glycolysis under LPS treatment. When T-cells and HCC cells were co-cultured with M1 macrophages, the reactivity of T cells was enhanced, and the level of Bax (an apoptosis-enhancer) was increased. At the same time, the expression of Bcl-2 (an apoptosis-suppressor) was suppressed.

Discussion

LPS-induced M1 macrophages exert antitumor effects through metabolic reprogramming and immune modulation, though further mechanistic studies are needed.

Conclusions

M1 macrophages inhibit HCC progression by activating T cells and inducing tumor cell apoptosis, offering novel insights for HCC immunotherapy.

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2025-07-11
2025-09-14

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References

  1. Gilles H. Garbutt T. Landrum J. Hepatocellular Carcinoma. Crit. Care Nurs. Clin. North Am. 2022 34 3 289 301 10.1016/j.cnc.2022.04.004 36049848
    [Google Scholar]
  2. Chandarana C.V. Mithani N.T. Singh D.V. Kikani U.B. Vibrational spectrophotometry: A comprehensive review on the diagnosis of gastric and liver cancer. Curr. Pharm. Anal. 2024 20 7 453 465 10.2174/0115734129322567240821052326
    [Google Scholar]
  3. Zhou Y. Gu J. Yu H. Chen F. Long C. Maihemuti M. Chen T. Zhang W. Screening and identification of ESR1 as a target of icaritin in hepatocellular carcinoma: Evidence from bibliometrics and bioinformatic analysis. Curr. Mol. Pharmacol. 2023 17 10.2174/0118761429260902230925044009 38239068
    [Google Scholar]
  4. Chidambaranathan-Reghupaty S. Fisher P.B. Sarkar D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv. Cancer Res. 2021 149 1 61 10.1016/bs.acr.2020.10.001 33579421
    [Google Scholar]
  5. Wang L. Wang J. Shi C. Wang W. Wu J. ABHD17C represses apoptosis and pyroptosis in hepatocellular carcinoma cells. Biocell 2024 48 9 1299 1310 10.32604/biocell.2024.051756
    [Google Scholar]
  6. Su F. Su W. Wang H. Wang Y. Ye L. Zhu P. Gu J. NMR-based metabolomic techniques identify the anticancer effects of three polyphyllins in HepG2 cells. Curr. Pharm. Anal. 2022 18 4 415 426 10.2174/1573412917666210823090145
    [Google Scholar]
  7. Finn R.S. Qin S. Ikeda M. Galle P.R. Ducreux M. Kim T.Y. Kudo M. Breder V. Merle P. Kaseb A.O. Li D. Verret W. Xu D.Z. Hernandez S. Liu J. Huang C. Mulla S. Wang Y. Lim H.Y. Zhu A.X. Cheng A.L. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020 382 20 1894 1905 10.1056/NEJMoa1915745 32402160
    [Google Scholar]
  8. El-Khoueiry A.B. Sangro B. Yau T. Crocenzi T.S. Kudo M. Hsu C. Kim T.Y. Choo S.P. Trojan J. Welling T.H. Meyer T. Kang Y.K. Yeo W. Chopra A. Anderson J. dela Cruz C. Lang L. Neely J. Tang H. Dastani H.B. Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017 389 10088 2492 2502 10.1016/S0140‑6736(17)31046‑2 28434648
    [Google Scholar]
  9. Sensi B. Angelico R. Toti L. Conte L.E. Coppola A. Tisone G. Manzia T.M. Mechanism, potential, and concerns of immunotherapy for hepatocellular carcinoma and liver transplantation. Curr. Mol. Pharmacol. 2024 17 18761429310703 10.2174/0118761429310703240823045808 39225204
    [Google Scholar]
  10. Dong L. Peng L. Ma L. Liu D. Zhang S. Luo S. Rao J. Zhu H. Yang S. Xi S. Chen M. Xie F. Li F. Li W. Ye C. Lin L. Wang Y. Wang X. Gao D. Zhou H. Yang H. Wang J. Zhu S. Wang X. Cao Y. Zhou J. Fan J. Wu K. Gao Q. Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma. J. Hepatol. 2020 72 5 896 908 10.1016/j.jhep.2019.12.014 31887370
    [Google Scholar]
  11. Han Q. Zhao H. Jiang Y. Yin C. Zhang J. HCC-derived exosomes: Critical player and target for cancer immune escape. Cells 2019 8 6 558 10.3390/cells8060558 31181729
    [Google Scholar]
  12. Villalba M. Rathore M.G. Lopez-Royuela N. Krzywinska E. Garaude J. Allende-Vega N. From tumor cell metabolism to tumor immune escape. Int. J. Biochem. Cell Biol. 2013 45 1 106 113 10.1016/j.biocel.2012.04.024 22568930
    [Google Scholar]
  13. Binnewies M. Roberts E.W. Kersten K. Chan V. Fearon D.F. Merad M. Coussens L.M. Gabrilovich D.I. Ostrand-Rosenberg S. Hedrick C.C. Vonderheide R.H. Pittet M.J. Jain R.K. Zou W. Howcroft T.K. Woodhouse E.C. Weinberg R.A. Krummel M.F. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 2018 24 5 541 550 10.1038/s41591‑018‑0014‑x 29686425
    [Google Scholar]
  14. Yang Z. Zi Q. Xu K. Wang C. Chi Q. Development of a macrophages-related 4-gene signature and nomogram for the overall survival prediction of hepatocellular carcinoma based on WGCNA and LASSO algorithm. Int. Immunopharmacol. 2021 90 107238 10.1016/j.intimp.2020.107238 33316739
    [Google Scholar]
  15. Wang T. Dai L. Shen S. Yang Y. Yang M. Yang X. Qiu Y. Wang W. Comprehensive molecular analyses of a macrophage-related gene signature with regard to prognosis, immune features, and biomarkers for immunotherapy in hepatocellular carcinoma based on WGCNA and the LASSO algorithm. Front. Immunol. 2022 13 843408 10.3389/fimmu.2022.843408 35693827
    [Google Scholar]
  16. Heymann F. Tacke F. Immunology in the liver — From homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol. 2016 13 2 88 110 10.1038/nrgastro.2015.200 26758786
    [Google Scholar]
  17. Sprinzl M.F. Reisinger F. Puschnik A. Ringelhan M. Ackermann K. Hartmann D. Schiemann M. Weinmann A. Galle P.R. Schuchmann M. Friess H. Otto G. Heikenwalder M. Protzer U. Sorafenib perpetuates cellular anticancer effector functions by modulating the crosstalk between macrophages and natural killer cells. Hepatology 2013 57 6 2358 2368 10.1002/hep.26328 23424039
    [Google Scholar]
  18. Murray P.J. Macrophage Polarization. Annu. Rev. Physiol. 2017 79 1 541 566 10.1146/annurev‑physiol‑022516‑034339 27813830
    [Google Scholar]
  19. Wildes T.J. Dyson K.A. Francis C. Wummer B. Yang C. Yegorov O. Shin D. Grippin A. Dean B.D. Abraham R. Pham C. Moore G. Kuizon C. Mitchell D.A. Flores C.T. Immune escape after adoptive T-cell therapy for malignant gliomas. Clin. Cancer Res. 2020 26 21 5689 5700 10.1158/1078‑0432.CCR‑20‑1065 32788225
    [Google Scholar]
  20. Shu Q.H. Ge Y.S. Ma H.X. Gao X.Q. Pan J.J. Liu D. Xu G.L. Ma J.L. Jia W.D. Prognostic value of polarized macrophages in patients with hepatocellular carcinoma after curative resection. J. Cell. Mol. Med. 2016 20 6 1024 1035 10.1111/jcmm.12787 26843477
    [Google Scholar]
  21. Tian Z. Hou X. Liu W. Han Z. Wei L. Macrophages and hepatocellular carcinoma. Cell Biosci. 2019 9 1 79 10.1186/s13578‑019‑0342‑7 31572568
    [Google Scholar]
  22. Chen H. Jiang S. Zhang P. Ren Z. Wen J. Exosomes synergized with PIONs@E6 enhance their immunity against hepatocellular carcinoma via promoting M1 macrophages polarization. Int. Immunopharmacol. 2021 99 107960 10.1016/j.intimp.2021.107960 34284286
    [Google Scholar]
  23. Zong Z. Zou J. Mao R. Ma C. Li N. Wang J. Wang X. Zhou H. Zhang L. Shi Y. M1 macrophages induce PD-L1 expression in hepatocellular carcinoma cells through IL-1β signaling. Front. Immunol. 2019 10 1643 10.3389/fimmu.2019.01643 31379842
    [Google Scholar]
  24. Jimenez-Duran G. Luque-Martin R. Patel M. Koppe E. Bernard S. Sharp C. Buchan N. Rea C. de Winther M.P.J. Turan N. Angell D. Wells C.A. Cousins R. Mander P.K. Masters S.L. Pharmacological validation of targets regulating CD14 during macrophage differentiation. EBioMedicine 2020 61 103039 10.1016/j.ebiom.2020.103039 33038762
    [Google Scholar]
  25. Malvicini R. Santa-Cruz D. De Lazzari G. Tolomeo A.M. Sanmartin C. Muraca M. Yannarelli G. Pacienza N. Macrophage bioassay standardization to assess the anti-inflammatory activity of mesenchymal stromal cell-derived small extracellular vesicles. Cytotherapy 2022 24 10 999 1012 10.1016/j.jcyt.2022.05.011 35798638
    [Google Scholar]
  26. Genin M. Clement F. Fattaccioli A. Raes M. Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer 2015 15 1 577 10.1186/s12885‑015‑1546‑9 26253167
    [Google Scholar]
  27. Li X. Shen H. Zhang M. Teissier V. Huang E.E. Gao Q. Tsubosaka M. Toya M. Kushioka J. Maduka C.V. Contag C.H. Chow S.K.H. Zhang N. Goodman S.B. Glycolytic reprogramming in macrophages and MSCs during inflammation. Front. Immunol. 2023 14 1199751 10.3389/fimmu.2023.1199751 37675119
    [Google Scholar]
  28. Wu Y. Ma J. Yang X. Nan F. Zhang T. Ji S. Rao D. Feng H. Gao K. Gu X. Jiang S. Song G. Pan J. Zhang M. Xu Y. Zhang S. Fan Y. Wang X. Zhou J. Yang L. Fan J. Zhang X. Gao Q. Neutrophil profiling illuminates anti-tumor antigen-presenting potency. Cell 2024 187 6 1422 1439.e24 10.1016/j.cell.2024.02.005 38447573
    [Google Scholar]
  29. Koppenhafer S.L. Goss K.L. Terry W.W. Gordon D.J. Inhibition of the ATR–CHK1 pathway in ewing sarcoma cells causes DNA damage and apoptosis via the CDK2-mediated degradation of RRM2. Mol. Cancer Res. 2020 18 1 91 104 10.1158/1541‑7786.MCR‑19‑0585 31649026
    [Google Scholar]
  30. Livak K.J. Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods 2001 25 4 402 408 10.1006/meth.2001.1262 11846609
    [Google Scholar]
  31. Tai Y. Wang Q. Korner H. Zhang L. Wei W. Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases. Front. Pharmacol. 2018 9 642 10.3389/fphar.2018.00642 29997500
    [Google Scholar]
  32. Woodhead V.E. Stonehouse T.J. Binks M.H. Speidel K. Fox D.A. Gaya A. Hardie D. Henniker A.J. Horejsi V. Sagawa K. Skubitz K.M. Taskov H. Todd R.F. van Agthoven A. Katz D.R. Chain B.M. Novel molecular mechanisms of dendritic cell-induced T cell activation. Int. Immunol. 2000 12 7 1051 1061 10.1093/intimm/12.7.1051 10882417
    [Google Scholar]
  33. Du W. Huang X. Liu R. Ye F. Li X. Sun B. Li H. Transcriptome analysis of tertiary lymphoid structures (TLSs)-related genes reveals prognostic value and immunotherapeutic potential in cancer. Oncologie 2024 26 2 287 300 10.1515/oncologie‑2023‑0372
    [Google Scholar]
  34. Klein C.A. Cancer progression and the invisible phase of metastatic colonization. Nat. Rev. Cancer 2020 20 11 681 694 10.1038/s41568‑020‑00300‑6 33024261
    [Google Scholar]
  35. Shirabe K. Mano Y. Muto J. Matono R. Motomura T. Toshima T. Takeishi K. Uchiyama H. Yoshizumi T. Taketomi A. Morita M. Tsujitani S. Sakaguchi Y. Maehara Y. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg. Today 2012 42 1 1 7 10.1007/s00595‑011‑0058‑8 22116397
    [Google Scholar]
  36. Mily A. FGF23 and fetuin-A interaction in the liver and in the circulation. Int. J. Biol. Sci. 2020 163 61807 10.3791/61807 33016941
    [Google Scholar]
  37. Han C. Yang Y. Sheng Y. Wang J. Zhou X. Li W. Guo L. Zhang C. Ye Q. Glaucocalyxin B inhibits cartilage inflammatory injury in rheumatoid arthritis by regulating M1 polarization of synovial macrophages through NF-κB pathway. Aging 2021 13 18 22544 22555 10.18632/aging.203567 34580236
    [Google Scholar]
  38. Zhang J. Liu Y. Chen H. Yuan Q. Wang J. Niu M. Hou L. Gu J. Zhang J. MyD88 in hepatic stellate cells enhances liver fibrosis via promoting macrophage M1 polarization. Cell Death Dis. 2022 13 4 411 10.1038/s41419‑022‑04802‑z 35484116
    [Google Scholar]
  39. Soskic B. Jeffery L.E. Kennedy A. Gardner D.H. Hou T.Z. Halliday N. Williams C. Janman D. Rowshanravan B. Hirschfield G.M. Sansom D.M. CD80 on human T cells is associated with FoxP3 expression and supports treg homeostasis. Front. Immunol. 2021 11 577655 10.3389/fimmu.2020.577655 33488578
    [Google Scholar]
  40. Wang N. Liang H. Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front. Immunol. 2014 5 614 10.3389/fimmu.2014.00614 25506346
    [Google Scholar]
  41. Zhang Y. Liang X. Bao X. Xiao W. Chen G. Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective. Eur. J. Med. Chem. 2022 235 114291 10.1016/j.ejmech.2022.114291 35307617
    [Google Scholar]
  42. Freitas M.S. Oliveira A.F. da Silva T.A. Fernandes F.F. Gonçales R.A. Almeida F. Roque-Barreira M.C. Paracoccin induces M1 polarization of macrophages via Interaction with TLR4. Front. Microbiol. 2016 7 1003 10.3389/fmicb.2016.01003 27458431
    [Google Scholar]
  43. Cutolo M. Campitiello R. Gotelli E. Soldano S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front. Immunol. 2022 13 867260 10.3389/fimmu.2022.867260 35663975
    [Google Scholar]
  44. Fujii J. Osaki T. Involvement of nitric oxide in protecting against radical species and autoregulation of M1-polarized macrophages through metabolic remodeling. Molecules 2023 28 2 814 10.3390/molecules28020814 36677873
    [Google Scholar]
  45. Sun S. Wu Y. Maimaitijiang A. Huang Q. Chen Q. Ferroptotic cardiomyocyte-derived exosomes promote cardiac macrophage M1 polarization during myocardial infarction. PeerJ 2022 10 13717 10.7717/peerj.13717 35818358
    [Google Scholar]
  46. Viola A. Munari F. Sánchez-Rodríguez R. Scolaro T. Castegna A. The Metabolic Signature of Macrophage Responses. Front. Immunol. 2019 10 1462 10.3389/fimmu.2019.01462 31333642
    [Google Scholar]
  47. Kelly B. O’Neill L.A.J. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res. 2015 25 7 771 784 10.1038/cr.2015.68 26045163
    [Google Scholar]
  48. Tannahill G.M. Curtis A.M. Adamik J. Palsson-McDermott E.M. McGettrick A.F. Goel G. Frezza C. Bernard N.J. Kelly B. Foley N.H. Zheng L. Gardet A. Tong Z. Jany S.S. Corr S.C. Haneklaus M. Caffrey B.E. Pierce K. Walmsley S. Beasley F.C. Cummins E. Nizet V. Whyte M. Taylor C.T. Lin H. Masters S.L. Gottlieb E. Kelly V.P. Clish C. Auron P.E. Xavier R.J. O’Neill L.A.J. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 2013 496 7444 238 242 10.1038/nature11986 23535595
    [Google Scholar]
  49. Rőszer T. Understanding the mysterious M2 macrophage through activation markers and Effector Mechanisms. Mediators Inflamm. 2015 2015 1 816460 10.1155/2015/816460 26089604
    [Google Scholar]
  50. Chen Y. Zhou Y. Yan Z. Tong P. Xia Q. He K. Effect of infiltrating immune cells in tumor microenvironment on metastasis of hepatocellular carcinoma. Cell. Oncol. 2023 46 6 1595 1604 10.1007/s13402‑023‑00841‑6 37414962
    [Google Scholar]
  51. Chen S. Saeed A.F.U.H. Liu Q. Jiang Q. Xu H. Xiao G.G. Rao L. Duo Y. Macrophages in immunoregulation and therapeutics. Signal Transduct. Target. Ther. 2023 8 1 207 10.1038/s41392‑023‑01452‑1 37211559
    [Google Scholar]
  52. Xu W. Cheng Y. Guo Y. Yao W. Qian H. Targeting tumor associated macrophages in hepatocellular carcinoma. Biochem. Pharmacol. 2022 199 114990 10.1016/j.bcp.2022.114990 35288152
    [Google Scholar]
  53. Yang Y. Guo J. Huang L. Tackling TAMs for cancer immunotherapy: It’s nano time. Trends Pharmacol. Sci. 2020 41 10 701 714 10.1016/j.tips.2020.08.003 32946772
    [Google Scholar]
  54. Ngambenjawong C. Gustafson H.H. Pun S.H. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Deliv. Rev. 2017 114 206 221 10.1016/j.addr.2017.04.010 28449873
    [Google Scholar]
  55. Xia Y. Rao L. Yao H. Wang Z. Ning P. Chen X. Engineering macrophages for cancer immunotherapy and drug delivery. Adv. Mater. 2020 32 40 2002054 10.1002/adma.202002054 32856350
    [Google Scholar]
  56. Wang X. Colorectal cancer-derived exosomes impair CD4(+) T cell function and accelerate cancer progression via macrophage activation. Cancer Biother. Radiopharm. 2024 40 3 185 195 10.1089/cbr.2024.0032 39263734
    [Google Scholar]
  57. Lopez P. Koh W.H. Hnatiuk R. Murooka T.T. HIV infection stabilizes macrophage-T cell interactions to promote cell-cell HIV spread. J. Virol. 2019 93 18 e00805 19 10.1128/JVI.00805‑19 31270227
    [Google Scholar]
  58. Najafi M. Hashemi Goradel N. Farhood B. Salehi E. Nashtaei M.S. Khanlarkhani N. Khezri Z. Majidpoor J. Abouzaripour M. Habibi M. Kashani I.R. Mortezaee K. Macrophage polarity in cancer: A review. J. Cell. Biochem. 2019 120 3 2756 2765 10.1002/jcb.27646 30270458
    [Google Scholar]
  59. Chen D. Xie J. Fiskesund R. Dong W. Liang X. Lv J. Jin X. Liu J. Mo S. Zhang T. Cheng F. Zhou Y. Zhang H. Tang K. Ma J. Liu Y. Huang B. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat. Commun. 2018 9 1 873 10.1038/s41467‑018‑03225‑9 29491374
    [Google Scholar]
  60. Luo X. O’Neill K.L. Huang K. The third model of Bax/Bak activation: A Bcl-2 family feud finally resolved? F1000 Res. 2020 9 935 10.12688/f1000research.25607.1 32802314
    [Google Scholar]
  61. Nguyen D. Osterlund E. Kale J. Andrews D.W. The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death. Biochem. J. 2024 481 14 903 922 10.1042/BCJ20210352 38985308
    [Google Scholar]
  62. Alam M. Alam S. Shamsi A. Adnan M. Elasbali A.M. Al-Soud W.A. Alreshidi M. Hawsawi Y.M. Tippana A. Pasupuleti V.R. Hassan M.I. Bax/Bcl-2 cascade is regulated by the EGFR pathway: Therapeutic targeting of non-small cell lung cancer. Front. Oncol. 2022 12 869672 10.3389/fonc.2022.869672 35402265
    [Google Scholar]
  63. Ma M. Wang X. Liu N. Shan F. Feng Y. Low-dose naltrexone inhibits colorectal cancer progression and promotes apoptosis by increasing M1-type macrophages and activating the Bax/Bcl-2/caspase-3/PARP pathway. Int. Immunopharmacol. 2020 83 106388 10.1016/j.intimp.2020.106388 32171145
    [Google Scholar]
  64. Lim W.T. Hong C.E. Lyu S.Y. Immuno-modulatory effects of Korean mistletoe in MDA-MB-231 breast cancer cells and THP-1 macrophages. Sci. Pharm. 2023 91 4 8 10.3390/scipharm91040048
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266394539250707102011
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Lipopolysaccharide-induced M1-type Macrophages Enhance T Cell Activity and Promote the Apoptosis of Hepatocellular Carcinoma Cells
Bentham Science Publishers ; https://doi.org/10.2174/0115680266394539250707102011
/content/journals/ctmc/10.2174/0115680266394539250707102011
/content/journals/ctmc/10.2174/0115680266394539250707102011
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  • Article Type:     Research Article
Keywords: Hepatocellular carcinoma ; Proliferation ; Macrophage ; Apoptosis ; T-cell activation ; Tumor microenvironment

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