膀癌固有的LRFN2通过减弱CD8+ T细胞透和功能过渡来驱动抗癌免疫疗法抵抗
Anze Yu1, Jiao Hu2, Liangmin Fu1
1Department of Urology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.
Journal for immunotherapy of cancer
|October 6, 2023
概括
富含白的重复和纤维素第3类域含有蛋白2 (LRFN2) 通过抑制CD8+T细胞活性,促进膀癌的免疫逃避. 向LRFN2可能会在晚期膀癌 (BLCA) 中增强免疫治疗反应.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 免疫检查点抑制剂 (ICI) 治疗为晚期膀癌 (BLCA) 提供了生存益处,但由于免疫疗法耐药性而面临限制.
- 在瘤微环境 (TME) 中,富含氨酸的重复和纤维素第3类域含有蛋白2 (LRFN2) 的作用及其对免疫疗法疗效的影响在很大程度上仍未明确.
研究的目的:
- 研究LRFN2在塑造瘤微环境 (TME) 的功能及其对膀癌 (BLCA) 免疫治疗反应的影响.
- 确定LRFN2作为克服BLCA免疫疗法耐药性的潜在治疗标.
主要方法:
- 使用了大量和单细胞RNA测序,ProcartaPlex免疫测试,体外和体内功能实验以及TissueFAXS全景组织量化的组合.
- 分析了LRFN2表达,免疫细胞透 (特别是CD8+ T细胞) 和临床免疫治疗反应数据之间的关系.
主要成果:
- 确定了LRFN2作为BLCA中一种新型的瘤内在免疫抑制因子,通过减少促炎性化学激素分泌来抑制CD8+T细胞的招募,透,增殖和功能过渡.
- 观察到LRFN2表达瘤细胞和CD8+T细胞之间的空间排除,以及PD-1和TCF-1标记物.
- 证明LRFN2的淘汰可以在临床前提高ICI治疗的疗效,LRFN2的表达可以预测临床队列中的免疫治疗反应.
结论:
- 在BLCA中,LRFN2通过调节TME和抑制CD8+T细胞介导的抗瘤免疫力,在瘤免疫逃避中发挥关键作用.
- LRFN2代表了与ICI结合治疗的有希望的治疗标,以改善晚期BLCA患者的治疗结果.
相关概念视频
01:27Tumor Immunotherapy
544
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
544
02:56Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
02:39lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
02:57Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K