医学英语视听学习丨肿瘤免疫学与免疫治疗

红牡丹gu1btzpv 2019-09-13

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Tumour immunology and immunotherapy

肿瘤免疫学与免疫治疗

Many genetic and environmental factors can cause tumors to form. For instance, UV radiation from the sun can damage DNA and other structures in melanocytes, which are the pigment producing cells in the skin. Chronic damage to melanocytes by UV radiation leads to most cases of melanoma, which is a type of skin cancer.

许多遗传和环境因素都会导致肿瘤形成。例如，黑色素细胞是产生皮肤色素的细胞，太阳紫外线辐射会破坏黑色素细胞的DNA和其它结构。长期紫外线辐射引起的黑色素细胞损伤是皮肤癌-黑色素瘤的主要病因。

As melanomas grow, they can eventually spread to other sites in the body, such as the lungs and liver. The cells of the immune system are continuously monitoring our tissues. Natural killer cells or NK cells send stress-associated molecules on damaged and cancerous cells. Dendritic cells or DCs activate cytotoxic T cells which can then send tumor-associated antigens using their T cell receptor and other co-receptors.

黑色素瘤不断生长，最终会扩散到身体其它部位，如肺和肝脏。免疫系统的细胞一直监视着我们的身体组织。自然杀伤细胞（NK细胞）向受损的癌变细胞释放应激相关分子（stress-associated molecules）。树突细胞（DC细胞）则会激活细胞毒性T细胞（CTL），然后CTL通过其T细胞受体和其他共同受体释放肿瘤相关抗原（TAA）。

Once activated, NK cells and cytotoxic T cells release perforin and granzymes. These molecules punch holes in the surface of the tumor cells causing them to die by apoptosis. Helper T cells support these responses. They help DCs to activate cytotoxic T cells and they produce cytokines, such as interferon γ that recruit and activate more NK cells.

一旦被激活，NK细胞和CTL便会释放穿孔素和颗粒酶。这些分子会在肿瘤细胞表面穿孔，使其逐渐凋亡。辅助性T细胞（Th）也促进这些反应。它们不仅能帮助DC细胞激活CTL，还会产生细胞因子，如γ干扰素，用于招募并激活更多NK细胞。

As the tumor evolves, genetic changes occur that can give some tumor cells a survival advantage, this means tumors are often heterogeneous. For instance, tumor cells may no longer express the molecules that are sensed by the killer immune cells. As the immune system continues to kill the tumor cells it can recognize, the cells that can't sense become more prevalent, this is immuno-editing, it leads to the emergence of a tumor that can't be detected by the immune system.

随着肿瘤不断进展，遗传变化会赋予某些肿瘤细胞以生存优势，即肿瘤通常具有异质性。例如，肿瘤细胞可能不再表达那些能够被杀伤性免疫细胞识别的分子。随着能够被免疫系统识别的肿瘤细胞不断被杀死，那些无法被识别的肿瘤细胞逐渐占据主导地位，这即是免疫编辑，这样最终会出现一种免疫系统无法识别的肿瘤。

Some tumor cells actively suppress T-cells by expressing inhibitory molecules such as PD-L1. PD-L1 binds to the PD-1 receptor on T-cells and deactivates them, this is an immune checkpoint. In addition, tumor cells can attract immune cells that suppress the activity of other immune cells, thereby supporting tumor growth. These immuno-suppressive cells include regulatory T-cells and certain types of myeloid cells. Therefore, the tumor microenvironment is like the scene of a battle between two opposing immune responses. One side of the immune system is attacking the tumor, while the other side is helping it to grow.

某些肿瘤细胞会表达抑制性分子，如PD-L1，来主动抑制T细胞。PD-L1与T细胞上的PD-1受体结合，使T细胞失活，这是其中一个免疫检查点。另外，肿瘤细胞还会吸引能够抑制其它免疫细胞活性的免疫细胞，从而促进肿瘤生长。这些免疫抑制细胞包括调节性T细胞和特定类型的髓系细胞。因此，肿瘤微环境就像两种对立免疫反应的战场：一方攻击肿瘤，另一方促进肿瘤生长。

Scientists are developing immunotherapies to help strengthen the immune attack. One approach is adoptive T-cell transfer. Cytotoxic T-cells taken from patients with melanoma are selected for their ability to attack tumor cells. The best killers are infused back into the patient. Treating patients with cytokines, such as interleukin 2 and interferon α can also boost the activity of anti-tumor immune cells. An alternative approach is to target the immune checkpoints. For instance, antibodies that bind to PD-1 stop this molecule from switching off cytotoxic T-cells. Another immune checkpoint being targeted is CTLA-4. Blocking this molecule helps DCs to drive anti-tumour T-cell responses.

科学家一直在研发能够增强免疫攻击的免疫疗法。一种方法是过继性T细胞转移，即提取黑色素瘤患者的CTL，并筛选能够攻击肿瘤细胞的CTL，然后把最具杀伤力的细胞回输至患者体内。应用白介素-2和α干扰素等细胞因子进行治疗也能增强抗肿瘤免疫细胞的活性。另一种可选方法是靶向免疫检查点治疗。例如，与PD-1结合的抗体会阻止该分子灭活CTL。另一个免疫检查点是CTLA-4。阻断CTLA-4有助于DC细胞激活抗肿瘤T细胞反应。

Not all patients will respond to these immunotherapies and some responses will be delayed. Combining immunotherapies with chemotherapy or radiotherapy can lead to a better response in some patients. Immunotherapies can themselves be combined, for example, PD-1 and CTLA-4 blockade can improve responses when administered in combination.

这些免疫疗法并不是对所有患者有效，有些患者的反应会延迟。免疫治疗联合化疗或放疗可能提高部分患者的反应。免疫疗法也可以联合应用，如PD-1和CTLA-4抑制剂联用可能提高患者反应。

Activating the immune system has risks. Some patients develop harmful side effects when their immune system attacks healthy cells. Nevertheless, there have been encouraging results from clinical trials. This animation has focused on melanoma, but it's becoming clear that immunotherapies can be used to treat many different types of cancer.

激活免疫系统具有风险。有些患者的免疫系统会攻击健康细胞，产生不良反应。不管怎样，临床试验已经取得了很多积极的结果。本视频主要聚焦黑色素瘤，但是很显然，免疫疗法可以用于治疗许多不同类型的癌症。

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