Mechanisms of Resistance to Anti-PD-1 Immunotherapy in Melanoma and Strategies to Overcome It

被引：3

作者：

Zielinska, Magdalena K. ^{[1
,2
]}

Ciazynska, Magdalena ^{[3
,4
]}

Sulejczak, Dorota ^{[5
]}

Rutkowski, Piotr ^{[1
]}

Czarnecka, Anna M. ^{[1
,5
]}

机构：

[1] Mar Sklodowska Curie Natl Res Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, PL-02781 Warsaw, Poland

[2] Warsaw Med Univ, Fac Med, PL-02091 Warsaw, Poland

[3] Specialised Oncol Hosp, Chemotherapy Unit & Day Chemotherapy Ward, PL-97200 Tomaszow Mazowiecki, Poland

[4] Med Univ Lodz, Dept Dermatol, Paediat Dermatol & Oncol Clin, PL-91347 Lodz, Poland

[5] Polish Acad Sci, Mossakowski Med Res Inst, Dept Expt Pharmacol, PL-02106 Warsaw, Poland

来源：

BIOMOLECULES | 2025年 / 15卷 / 02期

关键词：

melanoma; immunotherapy; nivolumab; pembrolizumab; primary resistance; secondary resistance; innate anti-PD-1 resistance signature (IPRES); melanoma immune evasion; anti-PD-1; anti-PD-1 therapy resistance; checkpoint inhibitors; REGULATORY T-CELLS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; PD-1; BLOCKADE; METASTATIC MELANOMA; IFN-GAMMA; FUSOBACTERIUM-NUCLEATUM; ACQUIRED-RESISTANCE; CHECKPOINT BLOCKADE; ANTITUMOR IMMUNITY; CLINICAL-RESPONSE;

D O I：

10.3390/biom15020269

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Resistance to anti-PD-1 therapy in melanoma remains a major obstacle in achieving effective and durable treatment outcomes, highlighting the need to understand and address the underlying mechanisms. The first key factor is innate anti-PD-1 resistance signature (IPRES), an expression of a group of genes associated with tumor plasticity and immune evasion. IPRES promotes epithelial-to-mesenchymal transition (EMT), increasing melanoma cells' invasiveness and survival. Overexpressed AXL, TWIST2, and WNT5a induce phenotypic changes. The upregulation of pro-inflammatory cytokines frequently coincides with EMT-related changes, further promoting a resistant and aggressive tumor phenotype. Inflamed tumor microenvironment may also drive the expression of resistance. The complexity of immune resistance development suggests that combination therapies are necessary to overcome it. Furthermore, targeting epigenetic regulation and exploring novel approaches such as miR-146a modulation may provide new strategies to counter resistance in melanoma.

引用

页数：24

共 164 条

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