md-medicaldata

Authors

 

Natali Rakočević¹, Nikola Aleksić¹, Jovana Drljača¹, Bojana Andrejić Višnjić¹, Nada Vučković², Ivan Čapo<sup>1

1</sup>Katedra za histologiju i embriologiju, Medicinski fakultet, Univerzitet u Novom Sadu
²Katedra za patologiju, Medicinski fakultet, Univerzitet u Novom Sadu.

 

UDK: 616.831-006

The paper was received / Rad primljen: 12.10.2020.

Accepted / Rad prihvaćen: 30.11.2020.

 

Correspondence to:

Natali Rakočević
Medicinski fakultet Univerziteta u Novom Sadu,
Hajduk Veljkova 3, 21000 Novi Sad, Republika Srbija.
e-mail: 1441d20@mf.uns.ac.rs

 

 

Sažetak

Glioblastom je najagresivniji primarni tumor centralnog nervnog sistema, i uprkos radikalnoj multimodalnoj terapiji, prosečno preživljavanje je veoma kratko. Jedna od histoloških karakteristika je prisustvo većeg broja GAM ćelija – glioblastom asocirane mikroglije/makrofaga. Usled hemoatraktanata koje sekretuje glioblastom, prvobitno dolazi do migracije rezidentne mikrogije okolnog moždanog parenhima, a kasnije i do infiltracije cirkulišućim monocitima. Ipak, ove ćelije urođenog imuniteta ne usporavaju dalju progresiju tumora. Uočena je sposobnost glioblastoma da menja fenotip GAM ćelija iz pro- u antiinflamatorni. Osim što ne napadaju tumorske ćelije, ove reprogramirane ćelije aktivno suprimiraju odgovor celularnog imuniteta. Ovaj imunološki beg dopušta glioblastomu dalju progresiju. Međutim, međusobni odnos mikroglije i tumorskih ćelija je znatno kompleksniji. Brojni radovi uspeli su da dokažu ulogu mikroglije u potenciranju proliferativnog, invazivnog i neoangiogenetskog potencijala glioblastoma. Posebno interesantni su rezultati koji identifikuju mikrogliju kao važan faktor u rezistenciji glioblastoma na radioterapiju i različite hemioterapeutike, što ukazuje na njen značaj u lošoj prognozi i preživljavanju pacijenata. Istovremeno međutim, modulacija funkcije mikroglije kao supstrata novih terapijskih modaliteta, mogla bi povećati senzitivnost glioblastoma na terapiju, a sledstveno i poboljšati stopu preživljavanja.

Ključne reči:

glioblastom; mikroglija; makrofagi; urođeni imunitet; mikrosredina tumora;

 

Abstract

Glioblastoma is the most aggressive primary central nervous system malignancy, and despite radical multimodal treatment, the average survival period is very short. One of the histological characteristics is the high number of GAM cells – glioblastoma associated microglia/macrophages. Through chemoattractants that glioblastoma secretes, initially, the resident microglia of surrounding brain tissue accumulates in the tumour. Later, the tumour is infiltrated by circulating monocytes. However, these innate immune cells are not able to slow down the tumour progression. It has been observed that glioblastoma can change the phenotype of GAM cells from pro- to anti-inflammatory. In addition to not attacking the tumour cells, these reprogrammed GAM cells strongly suppress the cellular immune response. This immune escape enables the further progression of glioblastoma. Relationship between microglia and tumour cells is much more complex, though. Numerous studies have shown the significant potentiating role of microglia in tumour proliferation, invasion and neoangiogenesis. Of particular interest are results that identified microglia as an essential factor for glioblastoma resistance to radiotherapy and chemotherapeutic agents, underlining its significance for bad prognosis and survival rate. On the other hand, modulating the microglia function as a new treatment target could potentially increase tumour sensitivity and therefore, the survival rate.

Keywords:

glioblastoma; microglia; macrophages; innate immunity; tumour microenvironment;

 

 

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