Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance

被引：39

作者：

Bell, Hannah N. ^{[1
,2
,3
]}

Zou, Weiping ^{[1
,2
,3
,4
]}

机构：

[1] Univ Michigan, Dept Surg, Med Sch, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Ctr Excellence Canc Immunol & Immunotherapy, Rogel Canc Ctr, Med Sch, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Grad Programs Canc Biol & Immunol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Pathol, Med Sch, Ann Arbor, MI USA

来源：

ANNUAL REVIEW OF IMMUNOLOGY | 2024年 / 42卷

基金：

美国国家卫生研究院;

关键词：

immune checkpoint blockade; tumor microenvironment; immunotherapy resistance; PD-1; PD-L1; CTLA-4; T cell; REGULATORY T-CELLS; IMMUNE CHECKPOINT BLOCKADE; CANCER-IMMUNOTHERAPY; PD-1; BLOCKADE; TUMOR MICROENVIRONMENT; SOLID TUMORS; DOUBLE-BLIND; LUNG-CANCER; COMBINATION IMMUNOTHERAPY; ACQUIRED-RESISTANCE;

D O I：

10.1146/annurev-immunol-101819-024752

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Immune checkpoint blockade (ICB) induces a remarkable and durable response in a subset of cancer patients. However, most patients exhibit either primary or acquired resistance to ICB. This resistance arises from a complex interplay of diverse dynamic mechanisms within the tumor microenvironment (TME). These mechanisms include genetic, epigenetic, and metabolic alterations that prevent T cell trafficking to the tumor site, induce immune cell dysfunction, interfere with antigen presentation, drive heightened expression of coinhibitory molecules, and promote tumor survival after immune attack. The TME worsens ICB resistance through the formation of immunosuppressive networks via immune inhibition, regulatory metabolites, and abnormal resource consumption. Finally, patient lifestyle factors, including obesity and microbiome composition, influence ICB resistance. Understanding the heterogeneity of cellular, molecular, and environmental factors contributing to ICB resistance is crucial to develop targeted therapeutic interventions that enhance the clinical response. This comprehensive overview highlights key mechanisms of ICB resistance that may be clinically translatable.

引用

页码：521 / 550

页数：30

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