Genomic and molecular alterations associated with primary resistance to immune checkpoint inhibitors

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-09-13 DOI:10.1007/s00262-024-03825-z
Jyoti Malhotra, Subhajyoti De, Kim Nguyen, Percy Lee, Victoria Villaflor
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Abstract

The clinical response to immune checkpoint inhibitors may vary by tumor type and many tumors present with either primary or acquired resistance to immunotherapy. Improved understanding of the molecular and immunologic mechanisms underlying immunotherapy resistance is essential for developing biomarkers and for guiding the optimum approach to selecting treatment regimens and sequencing. This is increasingly important for tumors with primary resistance as effective biomarkers in this setting can guide clinicians about appropriate treatment regimen selection in the first-line setting. Multiple potential biological mechanisms of primary resistance have been proposed but most are yet to be validated in prospective clinical cohorts. Individual biomarkers have poor specificity and sensitivity, and the development of validated and integrated predictive models may guide which patient will benefit from monotherapy versus combination therapy. In this review, we discuss the emerging data identifying the molecular mechanisms of primary resistance to immunotherapy and explore potential therapeutic strategies to target these.

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与免疫检查点抑制剂原发性耐药性相关的基因组和分子改变
不同类型的肿瘤对免疫检查点抑制剂的临床反应可能不同,许多肿瘤对免疫疗法存在原发性或获得性耐药性。进一步了解免疫疗法耐药性的分子和免疫学机制对于开发生物标记物、指导选择治疗方案和排序的最佳方法至关重要。这对于原发性耐药的肿瘤越来越重要,因为在这种情况下,有效的生物标志物可以指导临床医生在一线治疗中选择适当的治疗方案。目前已提出了多种原发性耐药的潜在生物机制,但大多数都有待在前瞻性临床队列中验证。单个生物标志物的特异性和敏感性较差,开发经过验证的综合预测模型可指导哪些患者将从单药治疗或联合治疗中获益。在本综述中,我们将讨论确定免疫疗法原发性耐药分子机制的新数据,并探讨针对这些机制的潜在治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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