Ćelije nalik supresorskim ćelijama mijeloidnog porekla – da li se njihov broj menja kod bolesnika u različitim stadijumima kolorektalnog karcinoma?

  • Irina Brčerević Military Medical Academy, Clinic for Gastroenterology and Hepatology, Belgrade, Serbia
  • Radoje Doder Military Medical Academy, Clinic for Gastroenterology and Hepatology, Belgrade, Serbia
  • Nenad Perišić Military Medical Academy, Clinic for Gastroenterology and Hepatology, Belgrade, Serbia
  • Stanko Petrović Military Medical Academy, Clinic for Gastroenterology and Hepatology, Belgrade, Serbia
  • Danilo Vojvodić Military Medical Academy, Institute for Medical Research, Belgrade, Serbia
Ključne reči: kolorektalne neoplazme, kostna srž, ćelije, supresorske, neoplazme, metastaze, neoplazme, određivanje stadijuma

Sažetak


Uvod/Cilj. Kolorektalni karcinom (KRK) je jedan od najčešćih karcinoma u populaciji, koji često dovodi i do smrtnog ishoda. Supresorske ćelije mijeloidnog porekla (SĆMP) pripadaju heterogenoj grupi nezrelih ćelija, za koje se smatra da imaju imunosupresivni efekat, koji može da pomogne razvoju i širenju tumora. Cilj rada bio je da se analizira učestalost i značaj ćelija nalik SĆMP kod bolesnika u različitim stadijumima KRK. Metode. Analizirani su uzorci periferne krvi (PK) 83 bolesnika u različitim stadijumima bolesti i 12 zdravih ispitanika koji su činili kontrolnu grupu. U uzorcima PK su, na osnovu imunofenotipskih obeležja, identifikovane ćelije nalik SĆMP i određen je njihov broj. Rezultati. Utvrđen je statistički značajan porast apsolutnog i relativnog broja ćelija nalik polimorfonuklearnim (PMN) SĆMP (PMN-SĆMP) u PK svih bolesnika sa KRK, u odnosu na kontrolnu grupu (< 0,0001). Kada nije vršeno poređenje prema stadijumima KRK, nije uočen statistički značajan porast broja ćelija nalik monocitnim SĆMP (M-SĆMP) (p > 0,05). Kada su analizirane relativne i apsolutne brojnosti ćelija nalik PMN-SĆMP u odnosu na stadijume bolesti KRK (TNM klasifikacija), utvrđena je statistički značajna razlika između kontrolne grupe i bolesnika u III i IV stadijumu bolesti (p = 0,0005 vs. p = 0,0003 i p < 0,0001 vs. < 0,0001, redom). Takođe, nađena je statistički značajna razlika brojnosti ćelija nalik PMN-SĆMP poređenjem bolesnika u I i II stadijumu bolesti, u odnosu na brojnost tih ćelija kod bolesnika u IV stadijumu KRK (p = 0,0161 vs. < 0,0001 i p = 0,0065 vs. p < 0,0001, redom). Statistički značajna razlika u relativnom i apsolutnom broju ćelija nalik M-SĆMP uočena je samo između bolesnika u II i IV stadijumu bolesti (p = 0,0014 i p = 0,0002, redom). Najveći broj ćelija nalik SĆMP uočen je u IV stadijumu bolesti, prema TNM klasifikaciji. Uočena je pozitivna korelacija između prisustva tih ćelija i broja organa koji su zahvaćeni metastatskim promenama (p < 0,0001 za relativni i apsolutni broj ćelija nalik PMN-SĆMP i p = 0,003, p = 0,0004 za relativni i apsolutni broj ćelija nalik M-SĆMP). Zaključak. Oboleli od KRK imali su statistički značajan porast broja ćelija nalik PMN-SĆMP u odnosu na zdrave ispitanike. Porast apsolutnih i relativnih vrednosti broja ovih ćelija većim delom prati rast i napredovanje KRK, dok je statistički značajna razlika broja ćelija nalik M-SĆMP uočena samo između II i IV stadijuma bolesti. Apsolutni i relativni broj oba podtipa ćelija sličnih SĆMP značajno koreliše sa brojem organa zahvaćenih metastazama u KRK.

Reference

1.      Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71(3): 209‒49.

2.      Bronte V, Serafini P, Apolloni E, Zanovello P. Tumor-induced immune dysfunctions caused by myeloid suppressor cells. J Immunother 2001; 24(6): 431–46.

3.      Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 2004; 4(12): 941‒52.

4.      Ostrand-Rosenberg S. Myeloid derived-suppressor cells: their role in cancer and obesity. Curr Opin Immunol 2018; 51: 68‒75.

5.      Gabrilovich D. Myeloid Derived Suppressor Cells. Cancer Immunol Res 2017; 5(1): 3‒8.

6.      Tcyganov E, Mastio  J, Chen  E, Gabrilovich DI. Plasticity of myeloid-derived suppressor cells in cancer. Curr Opin Immunol 2018; 51: 76‒82.

7.      Lu LC, Chang CJ, Hsu CH. Targeting myeloid-derived suppressor cells in the treatment of hepatocellular carcinoma: current state and future perspectives. J Hepatocell Carcinoma 2019; 6: 71–84. 

8.      Condamine T, Dominguez GA, Youn JI, Kossenkov AV, Mony S, Alicea-Torres K, et al. Lectin-type oxidized LDL receptor 1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 2016; 1(2): aaf8943.

9.      Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 2016; 7: 12150.

10.   Ma P, Beatty PL, McKolanis J, Brand R, Schoen RE, Finn OJ. Circulating Myeloid Derived Suppressor Cells (MDSC) That Accumulate in Premalignancy Share Phenotypic and Functional Characteristics With MDSC in Cancer. Front Immunol 2019; 10: 1401.

11.   Gabrilovich DNagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9(3): 162‒74.

12.   OuYang LY, Wu XJ, Ye SB, Zhang RX, Li ZL, Liao W, et al. Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer. J Transl Med 2015; 13: 47.

13.   Stanojević I, Miller K, Kandolf-Sekulović L, Mijušković Z, Zolotarevski L, Jović M, et al. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma. Int Immunol 2016; 28(2): 87‒97.

14.   Safarzadeh E, Hashemzadeh S, Duijf P, Mansoori B, Khaze V, Mohammadi A, et al. Circulating myeloid‐derived suppressor cells: An independent prognostic factor in patients with breast cancer. J Cell Physiol 2019; 234(4): 3515–25.

15.   Khaled YS, Ammori BJ, Elkord E. Increased Levels of Granulocytic Myeloid-Derived Suppressor Cells in Peripheral Blood and Tumour Tissue of Pancreatic Cancer Patients. J Immunol Res 2014; 2014: 879897.

16.   Yamauchi YSafi SBlattner C, Rathinasamy A, Umansky L, Juenger L, et al. Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non–Small Cell Lung Cancer.American Journal of Respiratory and Critical Care Medicine 2018; 198(6): 777–87.

17.   Cai W, Qin A, Guo P, Yan D, Hu F, Yang Q,  Hu FYang QXu M, et al. Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol 2013; 33(4): 798–808.

18.   Xi QLi YJuan DaiChen W. High frequency of mononuclear myeloid-derived suppressor cells is associated with exacerbation of inflammatory bowel disease. Immunol Invest 2015; 44(3): 279–87.

19.   Schrijver IT, Théroude C, Roger T. Myeloid-Derived Suppressor Cells in Sepsis. Front Immunol 2019; 10: 327.

20.   Vincent J, Mignot G, Chalmin F, Ladoire SBruchard MChevriaux A, et al. 5-Fluorouracil selectively kills Tumor-Associated Myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 2010; 70(8): 3052‒61.

21.   De Cicco P, Ercolano G, Ianaro A. The new era of cancer immunotherapy: Targeting Myeloid-derived suppressor cells to overcome immune evasion. Front Imunol 2020; 11: 1680.

22.   Yuan L, Xu B, Fan H, Yuan PZhao PSuo Z, et al. Pre- and post-operative evaluation: percentages of circulating myeloid-derived suppressor cells in rectal cancer patients. Neoplasma 2015; 62(2): 239‒49.

23.   Lee WC, Wang YC, Cheng CH, Wu TH, Lee CF, Wu TJ, et al. Myeloid-derived suppressor cells in the patients with liver resection for hepatitis B virus-related hepatocellular carcinoma. Sci Rep 2019; 9(1): 2269.

24.   Zhang B, Wang Z, Wu L, Zhang M, Li W, Ding J, et al. Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One 2013; 8(2): e57114.

25.   Toor SM, Khalaf S, Murshed K,  Abu Nada MElkord E. Myeloid cells in circulation and tumor microenvironment of Colorectal cancer patients with early and advanced disease stages. J Immunol Res 2020; 2020: 9678168.

26.   Hossaini F, Al-Khami AA, Wyczechowska D, Hernandez C, Zheng L, Reiss et K, et al. Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res 2015; 3(11): 1236–47.

27.   Karakasheva TA, Dominguez GA, Hashimoto A, Lin EW, Chiu CSasseret K, et al. CD38+ M-MDSC expansion characterizes a subset of advanced colorectal cancer patients. JCI Insight 2018; 3(6): e97022.

28.   Chouaib S, Umansky V, Kieda C. The role of hypoxia in shaping the recruitment of proangiogenic and immunosuppressive cells in the tumor microenvironment. Contemp Oncol (Pozn) 2018; 22(1A): 7–13.

29.   Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumors. Nat Rev Immunol 2012; 12(4): 253‒68.

30.   Condamine T, Mastio J, Gabrilovich DI. Transcriptional regulation of myeloid-derived suppressor cells. J Leukoc Biol 2015; 98(6): 913‒22.

31.   Milrud CR, Bergenfelz C, Leandersson K. On the origin of myeloid-derived suppressor cell. Oncotarget 2017; 8(2): 3649‒65.

32.   Shi H, Zhang J, Han X, Li H, Xie M, Sun Y, et al. Recruited monocytic myeloid-derived suppressor cells promote the arrest of tumor cells in the premetastatic niche through an IL-1beta-mediated increase in E-selectin expression. Int J Cancer 2017; 140(6): 1370–83.

33.   Limagne E, Euvrard R, Thibaudin M, Rébé C, Derangère VChevriaux A, et al. Accumulation of MDSC and Th17 cells in patient with metastatic colorectal cancer predicts the efficacy of a FOLFOX-bevacizumab drug treatment regimen. Cancer Res 2016; 76(18): 5241‒52.

34.   Fujita M, Kohanbash G, Fellows-Mayle W, Hamilton RL, Komohara Y, Decker SA, et al. COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 2011; 71(7): 2664‒74.

35.   Bauer R, Udonta F, Wroblewski M, Ben-Batalla I, Santos IM, Taverna F, et al. Blockade of myeloid-derived suppressor cells expansion with all trans retinoic acid increases the efficacy of antiangiogenic therapy. Cancer Res 2018; 78(12): 3220‒32.

36.   Walsh JE, Clark AM, Day TA, Gillespie MBYoung MR. Use of alpha 25-dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma. Hum Immunol 2010; 71(7): 659‒65.

37.   Lin S, Wang J, Wang L, Wen J, Guo Y, Qiaoet W, et al. Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC. Am J Cancer Res 2017; 7(1): 41‒52.

38.   Tavazioie MF, Pollack I, Tanqueco R, Ostendorf BN, Reis BS, Gonsalves FC, et al. LXR/ApoE activation restricts innate immune suppression in cancer. Cell 2018; 172(4): 825‒40.

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2023/08/01
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