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Cell:肿瘤免疫治疗综述

 3月10日,《细胞》杂志上发表的这篇题为“The Basis of Oncoimmunology”的综述中,作者讨论了癌症免疫响应的组成、癌症中慢性炎症和Leukocyte Compartments的改变、基于TH2的抗癌疗法、T细胞免疫靶向治疗、微生物在调节系统癌症风险和响应治疗中的作用以及肿瘤免疫治疗模式等内容。以下是文中的部分图表:

 The Makings of Tumor Immunity(图片来源:cell)


Immune-Mediated Landscape图片来源:cell)


The Priming of Cancer Immunity图片来源:cell)

 未来的免疫疗法将建立在干预循环(cycles of interventions)的基础上,这些干预措施旨在促进和调节抗癌免疫力。事实上,当我们逐渐重新认识和完善肿瘤免疫学的基础规律,越来越清楚的是,治愈癌症可能不是一个现实的目标。依据每位患者的肿瘤设计连续的治疗循环对改善治疗结果是非常必要的。

 检查点抑制剂的临床试验表明,原位免疫浸润对肿瘤消退至关重要;然而,并不是所有的免疫浸润都是相等的,免疫响应的质量是治疗成功的关键因素。细胞毒性治疗(如NK细胞、标准CTX/RT、溶瘤病毒)会产生neo-antigen,生成新一代的效应T细胞。需要强调的是,我们必须充分了解T细胞在人体内的作用规律。在以后的治疗中,neo-antigens的范围可能会扩大,除了体细胞突变,也能够通过表观遗传和翻译后调节形成。我们仍需要很长的时间来充分了解和解决这些问题。

参阅文献:

The Basis of Oncoimmunology

Cell, Volume 164, Issue 6, p1233–1247, 10 March 2016

Cancer heterogeneity, a hallmark enabling clonal survival and therapy resistance, is shaped by active immune responses. Antigen-specific T cells can control cancer, as revealed clinically by immunotherapeutics such as adoptive T-cell transfer and checkpoint blockade. The host immune system is thus a powerful tool that, if better harnessed, could significantly enhance the efficacy of cytotoxic therapy and improve outcomes for cancer sufferers. To realize this vision, however, a number of research frontiers must be tackled. These include developing strategies for neutralizing tumor-promoting inflammation, broadening T-cell repertoires (via vaccination), and elucidating the mechanisms by which immune cells organize tumor microenvironments to regulate T-cell activity. Such efforts will pave the way for identifying new targets for combination therapies that overcome resistance to current treatments and promote long-term cancer control.

 

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