毋庸置疑，免疫治疗已成为癌症精准医疗中的一大热点，并已逐步发展成为继手术、化疗和放疗后的第四种肿瘤治疗模式。至此跨年之际，Nature Reviews Clinical Oncology杂志以肿瘤免疫疗法为主题，精选了近年来肿瘤免疫研究中的经典图片。测序中国对其进行了编译整理，内容如下：
图1
肿瘤免疫系统是肿瘤免疫应答、免疫逃逸和肿瘤发生发展等相互关系的研究基础，对肿瘤的免疫诊断和防治有极其重要的作用。图1显示了肿瘤免疫系统中，来自适应性和先天免疫系统的多种免疫细胞类型。癌细胞可导致机体的免疫反应，癌症免疫周期主要包括：抗原生成，树突状细胞向T细胞呈递抗原，启动并激活针对癌症特异性抗原的效应T细胞，T细胞转运到肿瘤部位，癌细胞被识别并被杀死。
图片来源：
Hackl, H., Charoentong, P., Finotello, F.& Trajanoski, Z. Computational genomics tools for dissecting tumour–immune cell interactions. Nat. Rev.Genet. 17, 441–458 (2016)
图2
在免疫系统中，T淋巴细胞(简称T细胞)发挥着重要的免疫功能。T细胞表面存在诸多标记，如T细胞受体(TCR)、白细胞分化抗原(CD)等，根据T细胞表面TCR的类型，可将T细胞分为αβT细胞和γδT细胞两类。其中αβT细胞占T细胞总数的95%以上；γδT细胞数量较少，具有抗感染和抗肿瘤的作用。图2反应了γδT细胞的抗肿瘤功能及其调控。γδT细胞通过TCR和自然杀伤细胞受体（NKR）直接识别肿瘤细胞，通过各种机制介导肿瘤细胞死亡，包括产生抗体依赖性细胞毒性和干扰素-γ（IFNγ）。γδT细胞的抗肿瘤特性主要由白介素15（IL-15）、IL-2、IL-18和IL-21增强，其杀伤能力则受到肿瘤微环境中表观遗传药物或分子因素的抑制。
图片来源：
Silva-Santos, B., Mensurado, S. &Coffelt, S. B. γδT cells: pleiotropic immune effectors with therapeutic potential incancer. Nat. Rev. Cancer 19, 392–404 (2019)
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图3
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图4
图片来源：
Li, X. et al. Navigating metabolicpathways to enhance antitumour immunity and immunotherapy. Nat. Rev. Clin.Oncol. 16, 425–441 (2019)
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图5
根据T细胞的存在和分布，肿瘤可以分为四种主要的亚型：热肿瘤、冷肿瘤、免疫阻隔型肿瘤、免疫抑制型肿瘤。图5概述了已鉴定不同类型肿瘤的免疫图谱的主要成分、途径和特征（绿色），以及可以代表开发最成功治疗方案的潜在靶点（蓝色）。小写字母“ i”表示“抑制剂”；小写字母“ a”表示“激动剂”。
图片来源：
Gajewski, T. F., Schreiber, H. & Fu, Y.X. Innate and adaptive immune cells in the tumor microenvironment. Nat.Immunol. 14, 1014–1022 (2013)
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图6
图6概述了目前正在开发的用于治疗胶质母细胞瘤的不同免疫治疗方法，其中，包括依赖树突状细胞（DC）介导的胶质细胞瘤相关抗原的疫苗治疗；基于单克隆抗体的免疫检查点阻断药物；靶向肿瘤相关抗原的嵌合抗原受体（CAR）T细胞疗法；以及可在肿瘤细胞中选择性复制并诱导抗肿瘤免疫力病毒的溶瘤病毒疗法。
图片来源：
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图7
图片来源：
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图8
图片来源：
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图9
图片来源：
Sanli, O. et al. Bladder cancer. Nat.Rev. Disease Primers 3, 17022 (2017)
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图10
图片来源：
Riley, R. S., June, C. H., Langer, R.& Mitchell , M. J. Delivery technologies for cancer immunotherapy. Nat.Rev. Drug Discov. 18, 175–196 (2019)
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图11
图片来源：
Harrington, K., Freeman, D. J., Kelly,B., Harper , J. & Soria , J.-C. Optimizing oncolytic virotherapy in cancertreatment. Nat. Rev. Drug Discov. 18, 689–706 (2019)
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图12
图片来源：
Hackl, H., Charoentong, P., Finotello, F.& Trajanoski, Z. Computational genomics tools for dissecting tumour–immune cell interactions. Nat. Rev.Genet. 17, 441–458 (2016)
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图13
图13概述了嵌合抗原受体（CAR）T细胞疗法。从患者外周血中分离出CAR-T细胞，然后使用病毒或非病毒载体将编码CAR的基因插入到T细胞的基因组中。将工程化的T细胞在细胞培养物中增殖，然后重新注入患者体内。工程化T细胞表达的CAR将识别肿瘤细胞表面的抗原，进而激活T细胞，靶向消灭肿瘤细胞。
图片来源：
Feigal, E. G., DeWitt, N. D.,Cantilena, C., Peck , C. & Stroncek , D. At the end of the beginning:immunotherapies as living drugs. Nat. Immunology 20, 955–962 (2019)
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Jacoby, E. et al. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity. Nat. Commun. 7, 12320 (2016)
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