The tumour microenvironment:
Unlocking anti-tumour immunity

写的:

Dmitry Gabrilovich

Chief Scientist, Cancer 免疫学,
澳门在线赌城娱乐

西蒙·巴里

Executive Director, Head of tumour microenvironment, 澳门在线赌城娱乐

In our relentless quest for innovation, 澳门第一赌城在线娱乐努力获得疾病生物学的更深入的了解,目的是确定新的方法来靶向和治疗癌症. As we look towards the future of immuno-oncology (IO) therapies 澳门第一赌城在线娱乐正在研究癌细胞与免疫系统的相互作用, 肿瘤微环境(TME)在癌症进展中的作用.



What is the tumour microenvironment?

肿瘤在复杂的微环境中发展,促进了癌症形成的关键步骤, invasion and spread.1 这使得研究人员得出结论:“肿瘤微环境不仅仅是一个沉默的旁观者, but rather an active promoter of cancer progression" (Truffi et al., 2020), that can impact the success of a treatment.1 澳门第一赌城在线娱乐研究的一个方面集中在操纵TME以促进抗肿瘤免疫反应的潜力.2,3




Exploring the role of myeloid cells in the TME

骨髓细胞是人体先天免疫反应的重要组成部分,4 并在促进肿瘤细胞的识别和消除中发挥重要作用,同时使健康细胞不受伤害.5

在TME中, 具有免疫抑制特性的肿瘤相关骨髓细胞的积累与患者预后差和治疗耐药性有关, making them promising therapeutic targets.6 However, further research is required to unlock their potential.

随着澳门第一赌城在线娱乐对不同骨髓细胞群的作用有了更多的了解, 很明显,了解骨髓细胞的疾病分期和组织特异性作用对于开发针对骨髓的药物至关重要. 澳门第一赌城在线娱乐最近发表了一份对迄今为止的研究成果的全面回顾:6



髓样细胞有能力适应和反应不同的组织室, 这使得确定它们在癌症中的作用并针对它们进行治疗变得具有挑战性. Their plasticity reflects their native role, 在此期间,它们以一种敏捷的方式调节正在进行的免疫反应,并通过开启来优化宿主防御, 或抑制, pro-inflammatory pathways.7

在癌症, 这种可塑性有助于髓细胞分化为髓源性抑制细胞(MDSCs),这是发生在TME中的病理激活的一部分, enabling cancer cells to evade the immune system.7 In our recent publication we identify a new mechanism, lipid peroxidation, as a major driver behind this pathological activation.7



铁下垂对髓源性抑制细胞(MDSCs)的影响

With this knowledge, it is clear that we need to target myeloid cells early on, 在它们分化为MDSCs并产生免疫抑制特性之前.

Another promising new mechanism we are exploring is ferroptosis, 一种仅发生在TME的受调节细胞死亡,与脂质过氧化有关. Our research revealed that ferroptosis renders myeloid cells more immunosuppressive in mice, makes immune checkpoint inhibitors less effective.8

To our knowledge, 这是第一次提出铁下垂在癌症中的免疫抑制作用.
 

Learn more about how ferroptosis impacts cancer in the below video:

Therapeutic targeting of peroxynitrite from myeloid cells

一些癌症免疫疗法依赖于T细胞靶向癌细胞表面的特定抗原. We recently showed that a potent oxidant, known as peroxynitrite (PNT), produced by myeloid cells in the TME, 能否改变这些抗原,帮助癌细胞逃避免疫疗法.9

澳门第一赌城在线娱乐证明了 靶向治疗PNT可降低肿瘤对细胞毒性T细胞的耐药性 in mice, creating new avenues for designing novel cancer treatments.9
  

在以下视频中了解澳门第一赌城在线娱乐对靶向PNT生产以增强未来免疫疗法的想法:

The future of myeloid cells in shaping anti-tumour responses

As we learn more about myeloid cells, it helps to expand our knowledge of ways to target cancer, 例如,通过阻断髓细胞向TME的迁移,并通过限制它们与参与免疫监视的NK细胞的相互作用. Through these efforts, we hope to inform new drug combinations in the clinic, improve treatment responses in early disease.

Join us as we continue to explore the TME

We welcome committed, 才华横溢的科学家们加入澳门第一赌城在线娱乐,这将是最令人兴奋的事情之一, stimulating and rewarding journeys in 21st century medicine.

A leader in oncology with a global footprint, 澳门第一赌城在线娱乐正在发展一个差异化的管道,以解决与重大未满足需求相关的一系列肿瘤类型. 有无限的机会让你扬名立万,大胆冒险,开拓新思路. Diverse in experience and approach, 澳门第一赌城在线娱乐的团队有着追随科学的热情,为全球人民带来改变生活的药物.

澳门第一赌城在线娱乐招募具有相关专业知识的科学家加入澳门第一赌城在线娱乐最先进的研究设施 英国剑桥, 盖瑟斯堡, US.



主题:



参考文献

1. Anderson NM, Simon MC. The tumor microenvironment. 咕咕叫杂志. 2020;30:R921-R925.

2. Viswanadhapalli S, et al. Targeting LIF/LIFR signaling in cancer. 基因 & 疾病. 2021;9:973-980.

3. Nguyen KG, et al. Localized Interleukin-12 for Cancer Immunotherapy. 前面Immunol. 2020;11:575597. http://doi: 10.3389 / fimmu.2020.575597. Accessed March 2023. 

4. Schupp J, Krebs FK, Zimmer N, et al. Targeting myeloid cells in the tumor sustaining microenvironment. 细胞Immunol. 2019;343:103713. 

5. Neophytou CM, et al. 肿瘤相关髓系细胞在调节肿瘤治疗中的作用. 前肿瘤防治杂志. 2020;10:899.

6. Barry ST, Gabrilovich D, Sansom OJ, et al. Therapeutic targeting of tumour myeloid cells. 自然 Reviews Cancer. 2023. http://doi.org/10.1038/s41568-022-00546-2. Accessed March 2023. 

7. van Vlerken-Ysla L, Tyurina YY, Kagan VE, Gabrilovich DI. Functional states of myeloid cells in cancer. 癌症细胞. 2023; http://doi.org/10.1016/j.ccell.2023.02.009. Accessed March 2023. 

8. Kim R, Hashimoto A, Markosyan N, et al. 肿瘤中性粒细胞的铁下垂引起癌症的免疫抑制. 自然. 2022;612:338-346.

9. Tcyganov EN, Sanseviero E, Marvel D, et al. 肿瘤微环境中的过氧亚硝酸盐改变了抗原的轮廓,使其能够逃避癌症免疫治疗. 癌症细胞. 2022;10;40:1173-1189.


Veeva ID: Z4-51777
Date of preparation: March 2023