The advent of immune checkpoint inhibition has revolutionized treatment of advanced melanoma. While most patients derive survival benefit from established immunotherapies, notably monoclonal antibodies blocking cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1, a subset does not optimally respond due to the manifestation of innate or acquired resistance to these therapies. Combination regimens have proven efficacious relative to single-agent blockade, but also yield high-grade treatment toxicities that are often dose-limiting for patients. In this review, we discuss the significant strides made in the past half-decade toward expanding the melanoma immunotherapy treatment paradigm. These include newly approved therapies, adoption of neoadjuvant immunotherapy, and studies in the clinical trials pipeline targeting alternative immune checkpoints and key immunoregulatory molecules. We then review how developments in molecular and functional diagnostics have furthered our understanding of the tumor-intrinsic and -extrinsic mechanisms driving immunotherapy resistance, as well as highlight novel biomarkers for predicting treatment response. Throughout, we discuss potential approaches for targeting these resistance mechanisms in rational combination with established immunotherapies to improve outcomes for patients with melanoma.

David X. Zheng

David J. Bozym

Giuseppe Tarantino

Ryan J. Sullivan

David Liu

Russell W. Jenkins

American Journal of Clinical Dermatology

《美国临床皮肤病学杂志》通过发表涵盖皮肤病管理各个方面的批判性和综合性评论文章和以临床为重点的原创研究文章，促进皮肤病学学科内的循证治疗和有效的患者管理。美国临床皮肤病学杂志提供一系列额外的增强功能，旨在提高期刊内容的知名度、读者群和教育价值。每篇文章都附有一个关键点摘要，为广大读者提供了一个省时的内容概述。文章可能附有简单的语言摘要，以帮助患者、护理人员和其他人了解重要的医学进展。该杂志还提供了包含各种其他类型的增强功能的选项，包括幻灯片、视频和动画。所有增强功能都经过同行评审，达到与文章本身相同的高标准。同行评审是使用由国际专家数据库支持的 EDITORIAL MANAGER® 进行的。该数据库与其他 ADIS 期刊共享。

The American Journal of Clinical Dermatology aims to promote evidence-based treatment and effective patient management in the field of dermatology by publishing critical and comprehensive review articles, as well as clinically focused original research covering all aspects of skin disease management. The journal offers a range of additional enhancement features designed to increase the visibility, readership, and educational value of its content. Each article includes a key point summary, providing readers with a time-saving overview of the content. Articles may also include plain language summaries to help patients, caregivers, and others understand important medical advancements. The journal also provides options for various other types of enhancement features, including slides, videos, and animations. All enhancement features undergo peer review to meet the same high standards as the articles themselves. The peer review process is conducted using the EDITORIAL MANAGER®, supported by an international expert database that is shared with other ADIS journals.

《美国临床皮肤病学杂志》致力于通过发表涵盖皮肤病管理各个方面的批判性和综合性评论文章，以及以临床为重点的原创研究，推动皮肤病学领域的循证治疗和有效患者管理。该杂志提供多种增强功能，旨在提高期刊内容的知名度、读者群和教育价值。每篇文章都附有关键点摘要，方便读者快速了解内容。此外，文章可能还附有简单的语言摘要，以帮助患者、护理人员及其他相关人士理解重要的医学进展。杂志还提供包括幻灯片、视频和动画在内的多种增强功能选项，所有这些内容均经过同行评审，确保达到与文章本身相同的高标准。同行评审过程使用由国际专家数据库支持的 EDITORIAL MANAGER® 进行，该数据库与其他 ADIS 期刊共享。

Category	Quartile
医学	1
医学, 皮肤病学	1

Overcoming Resistance Mechanisms to Melanoma Immunotherapy

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