Expresia ligandu 1 programovanej smrti v nemalobunkovom karcinóme pľúc – mechanizmus regulácie, asociácia s ostatnými markermi a terapeutické využitie

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Autoři: V. Tancoš ¹; A. Blichárová ¹; L. Plank ^2,3
Působiště autorů: Ústav patológie UPJŠ LF a UNLP, Slovenská republika ¹; Ústav patologickej anatómie Jesseniovej lekárskej fakulty Univerzity Komenského a Univerzitnej nemocnice v Martine, Slovenská republika ²; Martinské bio ptické centrum, s. r. o. v Martin, Slovenská republika ³
Vyšlo v časopise: Klin Onkol 2022; 35(5): 372-376
Kategorie: Přehled
doi: https://doi.org/10.48095/ccko2022372

Souhrn

Východiská: Inhibítory imunitných kontrolných bodov (ICI) blokujúce signálnu dráhu proteínu 1 programovanej smrti (PD-1), dramaticky zlepšili prežívanie pacientov s pokročilým nemalobunkovým karcinómom pľúc (NSCLC). Imunohistochemická analýza expresie ligandu 1 programovanej smrti (PD-L1) je toho času najviac využívaným a klinicky validovaným biomarkerom predikujúcim efektívnosť ICI u pacientov s NSCLC, ale sám o sebe predstavuje nedokonalý nástroj. Signálna dráha PD-1 je poprepájaná s početnými celulárnymi ako aj molekulárnymi faktormi prítomnými v nádorovom mikroprostredí (TME) v NSCLC. Celulárne faktory, ktoré sa podieľajú na regulácii expresie PD-L1 v NSCLC sú pripisované aktivite nádor infiltrujúcich lymfocytov a s nádorom asociovanými fibroblastmi. Vnútorné molekulárne faktory, ktoré majú vplyv na úroveň expresie PD-L1 v NSCLC, sú asociované s prítomnosťou onkogénnych driver mutácií v génoch receptora epidermálneho rastového faktora a v homológu virového onkogénu Kirsten rat sarcoma a s translokáciami vedúcimi k prestavbe kinázy anaplastického lymfómu. Okrem toho, na úroveň expresie PD-L1 v NSCLC môže mať vplyv aj stimulácia hypoxických signálnych dráh a aktivácia transformujúceho rastového faktora beta 1. Hlbšie pochopenie zložitých mechanizmov regulujúcich expresiu PD-L1 je nevyhnutné, aby bolo v budúcnosti možné ušiť na mieru terapiu s použitím ICI u pacientov s pokročilým NSCLC. Cieľ: V predkladanom prehľadovom článku prezentujeme súhrn kľúčových faktorov podieľajúcich sa na regulácii expresie PD-L1 v rámci TME v NSCLC, ktoré sú a potenciálne môžu byť využívané za účelom zlepšenia účinnosti imunoterapie, ktorá blokuje signálnu dráhu PD-1.

Klíčová slova:

nemalobunkový karcinóm pľúc – tumor infiltrujúce lymfocyty – inhibítory imunitných kontrolných bodov – proteínu 1 programovanej smrti – ligand 1 programovanej bunkovej smrti – epitelovo mezenchýmový prechod – hypoxiou indukovateľný faktor-1α

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