缺氧作为免疫耐受、肿瘤可塑性和肿瘤突变负担的潜在诱导剂:对癌症免疫治疗的影响。

IF 12.1 1区 医学 Q1 ONCOLOGY Seminars in cancer biology Pub Date : 2023-12-01 DOI:10.1016/j.semcancer.2023.11.008
Raefa Abou Khouzam , Bassam Janji , Jerome Thiery , Rania Faouzi Zaarour , Ali N. Chamseddine , Hemma Mayr , Pierre Savagner , Claudine Kieda , Sophie Gad , Stéphanie Buart , Jean–Marie Lehn , Perparim Limani , Salem Chouaib
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引用次数: 0

摘要

在癌症患者中,由于肿瘤微环境(TME)的免疫抑制特征,免疫细胞往往功能受损,导致癌症治疗失败。临床和实验证据表明,发育中的肿瘤通过诱导免疫耐受和侵袭来适应免疫环境,并在局部形成损害免疫功能的微环境。在这种情况下,微环境缺氧作为实体瘤的一个既定标志,通过诱导肿瘤可塑性/异质性,更重要的是通过免疫抑制性基质细胞的分化和扩增,显著促进肿瘤的侵袭性和治疗耐药性。我们和其他人提供的证据表明,缺氧也会导致癌细胞的基因组不稳定,并干扰DNA损伤反应和修复,这表明缺氧可能是肿瘤突变负担的潜在驱动因素。在这里,我们回顾了目前关于TME缺氧应激如何影响肿瘤血管生成、异质性、可塑性和免疫抵抗的知识,特别关注肿瘤免疫原性和缺氧靶向性。对缺氧对免疫和微环境成分影响的复杂性的综合理解可能导致在癌症免疫治疗中确定更好的适应性和更有效的组合策略。显然,从低氧肿瘤微环境中发现和验证治疗靶点是非常重要的,并且确定关键的低氧相关通路可以产生对联合癌症免疫治疗方法具有不可否认的吸引力的靶点。
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Hypoxia as a potential inducer of immune tolerance, tumor plasticity and a driver of tumor mutational burden: Impact on cancer immunotherapy

In cancer patients, immune cells are often functionally compromised due to the immunosuppressive features of the tumor microenvironment (TME) which contribute to the failures in cancer therapies. Clinical and experimental evidence indicates that developing tumors adapt to the immunological environment and create a local microenvironment that impairs immune function by inducing immune tolerance and invasion. In this context, microenvironmental hypoxia, which is an established hallmark of solid tumors, significantly contributes to tumor aggressiveness and therapy resistance through the induction of tumor plasticity/heterogeneity and, more importantly, through the differentiation and expansion of immune-suppressive stromal cells. We and others have provided evidence indicating that hypoxia also drives genomic instability in cancer cells and interferes with DNA damage response and repair suggesting that hypoxia could be a potential driver of tumor mutational burden. Here, we reviewed the current knowledge on how hypoxic stress in the TME impacts tumor angiogenesis, heterogeneity, plasticity, and immune resistance, with a special interest in tumor immunogenicity and hypoxia targeting. An integrated understanding of the complexity of the effect of hypoxia on the immune and microenvironmental components could lead to the identification of better adapted and more effective combinational strategies in cancer immunotherapy. Clearly, the discovery and validation of therapeutic targets derived from the hypoxic tumor microenvironment is of major importance and the identification of critical hypoxia-associated pathways could generate targets that are undeniably attractive for combined cancer immunotherapy approaches.

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来源期刊
Seminars in cancer biology
Seminars in cancer biology 医学-肿瘤学
CiteScore
26.80
自引率
4.10%
发文量
347
审稿时长
15.1 weeks
期刊介绍: Seminars in Cancer Biology (YSCBI) is a specialized review journal that focuses on the field of molecular oncology. Its primary objective is to keep scientists up-to-date with the latest developments in this field. The journal adopts a thematic approach, dedicating each issue to an important topic of interest to cancer biologists. These topics cover a range of research areas, including the underlying genetic and molecular causes of cellular transformation and cancer, as well as the molecular basis of potential therapies. To ensure the highest quality and expertise, every issue is supervised by a guest editor or editors who are internationally recognized experts in the respective field. Each issue features approximately eight to twelve authoritative invited reviews that cover various aspects of the chosen subject area. The ultimate goal of each issue of YSCBI is to offer a cohesive, easily comprehensible, and engaging overview of the selected topic. The journal strives to provide scientists with a coordinated and lively examination of the latest developments in the field of molecular oncology.
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