Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy.
Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy.
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利用肿瘤坏死因子α实现有效的癌症免疫治疗。
DOI：
10.3390/cancers13030564
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发表时间：
2021-02-02
期刊：
影响因子：
5.2
通讯作者：
Schillaci R
中科院分区：
文献类型：
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作者：
Mercogliano MF;Bruni S;Mauro F;Elizalde PV;Schillaci R
炎症被认为是癌症风险增加的原因之一。在促炎介质中，肿瘤坏死因子α（TNFα）已被确定为癌症进展和转移的重要参与者。另一方面，TNFα在促进先天性和适应性免疫应答中具有核心作用。通过对TNF α亚型和TNFα受体不同作用机制的不同研究，这些明显有争议的作用现在开始被发现。免疫疗法用于癌症治疗，如抗癌细胞的单克隆抗体或免疫检查点和过继细胞治疗，开始拓宽我们对TNFα作用及其潜在治疗作用的理解。这项工作描述了TNFα参与作为治疗耐药性的来源及其在免疫治疗副作用中的意义，以及其在不同癌症类型中的参与，其中TNFα可以成为改善治疗结果的合适靶点。肿瘤坏死因子α（TNFα）是一种多效性细胞因子，已知在肿瘤免疫学中具有相互矛盾的作用。事实上，TNFα在免疫应答的发生中具有核心作用，诱导巨噬细胞、树突状细胞、自然杀伤（NK）细胞以及B和T淋巴细胞的活化和效应功能。然而，在肿瘤微环境中，TNFα是癌症相关炎症的主要介质之一。它参与免疫抑制细胞的募集和分化，导致逃避肿瘤免疫监视。这些特性使TNFα成为克服治疗耐药性和治疗癌症的有吸引力的靶点。本文综述了TNFα作为免疫治疗（如抗癌细胞的单克隆抗体或免疫检查点）和过继细胞治疗耐药来源的不同分子机制。我们还揭示了TNFα阻断策略与免疫治疗联合使用的益处，以提高抗肿瘤作用并预防或治疗不良免疫相关作用。
Inflammation has been acknowledged as one of the causes of increased cancer risk. Among the pro-inflammatory mediators, tumor necrosis factor alpha (TNFα) has been identified as an important player in cancer progression and metastasis. On the other hand, TNFα has a central role in promoting innate and adaptive immune responses. These apparently controversial effects are now starting to be uncovered through different studies on TNFɑ isoforms and distinct mechanisms of action of TNFα receptors. The use of immunotherapies for cancer treatment such as monoclonal antibodies against cancer cells or immune checkpoints and adoptive cell therapy, are beginning to broaden our understanding of TNFα’s actions and its potential therapeutic role. This work describes TNFα participation as a source of treatment resistance and its implication in side effects to immunotherapy, as well as its participation in different cancer types, where TNFα can be a suitable target to improve therapy outcome. Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine known to have contradictory roles in oncoimmunology. Indeed, TNFα has a central role in the onset of the immune response, inducing both activation and the effector function of macrophages, dendritic cells, natural killer (NK) cells, and B and T lymphocytes. Within the tumor microenvironment, however, TNFα is one of the main mediators of cancer-related inflammation. It is involved in the recruitment and differentiation of immune suppressor cells, leading to evasion of tumor immune surveillance. These characteristics turn TNFα into an attractive target to overcome therapy resistance and tackle cancer. This review focuses on the diverse molecular mechanisms that place TNFα as a source of resistance to immunotherapy such as monoclonal antibodies against cancer cells or immune checkpoints and adoptive cell therapy. We also expose the benefits of TNFα blocking strategies in combination with immunotherapy to improve the antitumor effect and prevent or treat adverse immune-related effects.
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影响因子：
5.7
作者：
Aida K;Miyakawa R;Suzuki K;Narumi K;Udagawa T;Yamamoto Y;Chikaraishi T;Yoshida T;Aoki K
通讯作者：
Aoki K
DOI：
10.1186/s13046-018-0751-1
发表时间：
2018-04-20
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Aurisicchio L;Pallocca M;Ciliberto G;Palombo F
通讯作者：
Palombo F
影响因子：
7.3
作者：
Banzola I;Mengus C;Wyler S;Hudolin T;Manzella G;Chiarugi A;Boldorini R;Sais G;Schmidli TS;Chiffi G;Bachmann A;Sulser T;Spagnoli GC;Provenzano M
通讯作者：
Provenzano M
影响因子：
4.4
作者：
Bauswein, Markus;Singh, Anurag;Rieber, Nikolaus
通讯作者：
Rieber, Nikolaus
影响因子：
8.8
作者：
通讯作者：
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